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1.
Chinese Journal of Contemporary Pediatrics ; (12): 179-185, 2023.
Article in Chinese | WPRIM | ID: wpr-971057

ABSTRACT

OBJECTIVES@#To investigate the changes and significance of type 2 innate lymphoid cells (ILC2), interleukin-33 (IL-33), interleukin-25 (IL-25), thymic stromal lymphopoietin (TSLP), interleukin-5 (IL-5), and interleukin-13 (IL-13) in peripheral blood of preterm infants with bronchopulmonary dysplasia (BPD).@*METHODS@#A total of 76 preterm infants with a gestational age of <32 weeks and a length of hospital stay of ≥14 days who were admitted to the Department of Pediatrics of the Affiliated Hospital of Jiangsu University from September 2020 to December 2021 were enrolled. According to the diagnostic criteria for BPD, they were divided into a BPD group with 30 infants and a non-BPD group with 46 infants. The two groups were compared in terms of the percentage of ILC2 and the levels of IL-33, IL-25, TSLP, IL-5, and IL-13 in peripheral blood on days 1, 7, and 14 after birth.@*RESULTS@#The BPD group had significantly lower birth weight and gestational age than the non-BPD group (P<0.05). On days 7 and 14 after birth, the BPD group had significantly higher levels of ILC2, IL-33, TSLP, and IL-5 than the non-BPD group (P<0.05), and these indices had an area under the curve of >0.7 in predicting the devolpment of BPD (P<0.05). Multivariate logistic regression analysis showed that after adjusting for gestational age and birth weight, peripheral blood IL-33, TSLP and IL-5 on days 7 and 14 after birth were closely related to the devolpment of BPD (P<0.05).@*CONCLUSIONS@#Early innate immune activation and upregulated expression of related factors may be observed in preterm infants with BPD. ILC2, IL-33, TSLP, and IL-5 may be used as biological indicators for early diagnosis of BPD.


Subject(s)
Child , Humans , Infant , Infant, Newborn , Birth Weight , Bronchopulmonary Dysplasia/pathology , Cytokines , Immunity, Innate , Infant, Premature , Interleukin-13 , Interleukin-33 , Interleukin-5 , Lymphocytes/pathology , Thymic Stromal Lymphopoietin
2.
Chinese Journal of Cellular and Molecular Immunology ; (12): 599-603, 2023.
Article in Chinese | WPRIM | ID: wpr-981905

ABSTRACT

Objective To investigate the relationship between intestinal inflammatory group 2 innate lymphoid cells (iILC2s) and lung ILC2s and its inflammatory response in chronic obstructive pulmonary disease (COPD). Methods Mouse COPD model was established by smoking method. The mice were randomly divided into normal group and COPD group. HE staining was used to detect the pathological changes in lung and intestine tissues of mice in normal group and COPD group, and the contents of natural ILC2s(nILC2s) and iILC2s cells were measured by flow cytometry. Wright-Giemsa staining was used to measure the number of immune cells in the bronchoalveolar lavage fluid (BALF) of mice in normal group and COPD group, and the concentration of IL-13 and IL-4 was detected by ELISA. Results In COPD mice, epithelial cells of the lung and intestinal tissues exhibited pathological hyperplasia, partial atrophy or deletion, inflammatory cell infiltration, increased pathological score and significantly increased neutrophils, monocytes, and lymphocytes in BALF. Lung iILC2s, intestinal nILC2s and iILC2s were increased significantly in the COPD group. The contents of IL-13 and IL-4 in BALF were significantly increased. Conclusion The increase of iILC2s and their related cytokines in COPD lung may be related to intestinal inflammatory ILC2s.


Subject(s)
Mice , Animals , Cytokines , Immunity, Innate , Interleukin-13 , Interleukin-4 , Lymphocytes , Lung/pathology , Pulmonary Disease, Chronic Obstructive , Bronchoalveolar Lavage Fluid , Disease Models, Animal , Intestines
3.
Chinese Journal of Cellular and Molecular Immunology ; (12): 1094-1099, 2023.
Article in Chinese | WPRIM | ID: wpr-1009460

ABSTRACT

Objective To investigate the effect of calcitonin gene-related peptide (CGRP) on the regulation of group 2 innate lymphoid cells (ILC2) in the peripheral blood of patients with allergic rhinitis (AR). Methods Peripheral blood mononuclear cells (PBMCs) were extracted from normal healthy individuals and AR patients, then stimulated with CGRP, interleukin 33 (IL-33) and CGRP combined with IL-33 for 3 days, with blank stimulus as control. The percentage of ILC2 in the four groups was measured by flow cytometry. After being sorted, ILC2 was given to CGRP, IL-33 and CGRP combined with IL-33 stimulation for 3 days, with blank stimulus as control. The percentage of IL-5 and IL-13 positive cells in ILC2 was detected by flow cytometry, and the levels of IL-5 and IL-13 in ILC2 supernatant were measured by ELISA. Results The percentage of ILC2 in the peripheral blood of AR patients was significantly higher than that of the control group. The levels of IL-5+ILC2 and IL-13+ILC2 were significantly increased by IL-33 single stimulation after culturing PBMCs. After adding IL-33 combined with CGRP stimulation, the levels of IL-5+ILC2 and IL-13+ILC2 in PBMCs were significantly reduced; after CGRP single stimulation, the levels of IL-5+ILC2 and IL-13+ILC2 in PBMCs were further decreased. After ILC2 was sorted and cultured, the levels of IL-5+ILC2 and IL-13+ILC2 showed significant increase after IL-33 single stimulation. The levels of IL-5+ILC2 and IL-13+ILC2 were decreased by IL-33 and CGRP co-stimulation, and they were further reduced after CGRP single stimulation. Compared to IL-33 single stimulation, IL-5 and IL-13 levels dropped significantly due to the IL-33 and CGRP co-stimulation. The levels of IL-5 and IL-13 were further reduced by CGRP single stimulation. Conclusion CGRP inhibits the proliferation and activation of peripheral blood ILC2 in AR and exert anti-inflammatory effects in AR.


Subject(s)
Humans , Calcitonin Gene-Related Peptide/pharmacology , Leukocytes, Mononuclear , Immunity, Innate , Interleukin-33/pharmacology , Interleukin-13 , Lymphocytes , Interleukin-5/pharmacology , Rhinitis, Allergic , Cell Proliferation
4.
International Journal of Oral Science ; (4): 29-29, 2022.
Article in English | WPRIM | ID: wpr-939848

ABSTRACT

Immunoglobulin G4-related sialadenitis (IgG4-RS) is an immune-mediated fibro-inflammatory disease and the pathogenesis is still not fully understood. The aim of this study was to explore the role and mechanism of interleukin-13 (IL-13) in the cellular senescence during the progress of IgG4-RS. We found that the expression of IL-13 and IL-13 receptor α1 (IL-13Rα1) as well as the number of senescent cells were significantly higher in the submandibular glands (SMGs) of IgG4-RS patients. IL-13 directly induced senescence as shown by the elevated activity of senescence-associated β-galactosidase (SA-β-gal), the decreased cell proliferation, and the upregulation of senescence markers (p53 and p16) and senescence-associated secretory phenotype (SASP) factors (IL-1β and IL-6) in SMG-C6 cells. Mechanistically, IL-13 increased the level of phosphorylated signal transducer and activator of transcription 6 (p-STAT6) and mitochondrial-reactive oxygen species (mtROS), while decreased the mitochondrial membrane potential, ATP level, and the expression and activity of superoxide dismutase 2 (SOD2). Notably, the IL-13-induced cellular senescence and mitochondrial dysfunction could be inhibited by pretreatment with either STAT6 inhibitor AS1517499 or mitochondria-targeted ROS scavenger MitoTEMPO. Moreover, IL-13 increased the interaction between p-STAT6 and cAMP-response element binding protein (CREB)-binding protein (CBP) and decreased the transcriptional activity of CREB on SOD2. Taken together, our findings revealed a critical role of IL-13 in the induction of salivary gland epithelial cell senescence through the elevated mitochondrial oxidative stress in a STAT6-CREB-SOD2-dependent pathway in IgG4-RS.


Subject(s)
Humans , Cellular Senescence/genetics , Immunoglobulin G/metabolism , Interleukin-13/pharmacology , Mitochondria/metabolism , Sialadenitis/metabolism
5.
Arq. Asma, Alerg. Imunol ; 5(4): 416-421, out.dez.2021. ilus
Article in English, Portuguese | LILACS | ID: biblio-1399806

ABSTRACT

A dermatite atópica (DA) é uma doença inflamatória crônica da pele, caracterizada por intenso prurido e eczema recorrente. Acomete principalmente a infância, mas tem se tornado bastante prevalente em adolescentes e até em adultos. Apesar de ser geralmente não fatal, apresenta uma carga psicossocial importante para os pacientes e seus familiares. O tratamento da DA envolve a hidratação cutânea e medicações anti-inflamatórias. Em casos graves, pode haver necessidade de terapia sistêmica com imunossupressores como ciclosporina, metotrexato e azatioprina. Mais recentemente, alguns imunobiológicos estão em desenvolvimento para controle da DA. O dupilumabe é um anticorpo monoclonal com ação dupla anti-IL-4/IL-13, liberado para tratamento de crianças a partir de 6 anos com DA grave e adolescentes/adultos com DA moderada a grave. O objetivo deste artigo foi relatar uma série de casos de pacientes adolescentes e adultos com DA grave e sua resposta ao dupilumabe durante a pandemia do COVID-19. Trata-se de quatro pacientes (três do sexo feminino), com piora significativa da DA durante o ano de 2020. Todos tinham história de DA desde a infância, com exames complementares evidenciando sensibilização IgE-mediada para ácaros. Já haviam sido submetidos a diversos tratamentos tópicos e sistêmicos, inclusive a cursos de corticosteroides orais. Nenhum deles havia recebido imunossupressor sistêmico, porém estavam recusando este tipo de tratamento devido ao medo da pandemia. Todos apresentaram boa resposta ao dupilumabe, evidenciada pela redução do número de lesões cutâneas e prurido, com poucos efeitos colaterais. Dois pacientes apresentaram sintomas sugestivos de COVID-19 durante o tratamento com dupilumabe (um com confirmação por PCR), com boa evolução. Concluindo, os pacientes com DA grave possuem grande impacto na qualidade de vida e, durante a pandemia de COVID-19, muitos apresentaram piora significativa do seu quadro dermatológico. Nesse contexto, o dupilumabe se mostrou uma opção terapêutica eficaz e segura para tratamento destes pacientes.


Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by intense itching and recurrent eczema. It mainly affects childhood but has become quite prevalent in adolescents and even adults. Despite being generally nonfatal, it has an important psychosocial burden for patients and their families. AD treatment involves skin hydration and antiinflammatory medications. In severe cases, systemic therapy with immunosuppressive agents such as cyclosporine, methotrexate, and azathioprine may be necessary. More recently, some biologicals are being developed to control AD. Dupilumab is a monoclonal antibody with anti-IL-4/IL-13 dual-action, approved for the treatment of children from 6 years of age with severe AD and adolescents/adults with moderate to severe AD. This article aimed to report a case series of adolescent and adult patients with severe AD and their response to dupilumab during the COVID-19 pandemic. These are four patients (three female), with a significant worsening of AD during the year 2020. All had a history of AD since childhood, with complementary exams showing IgE-mediated sensitization to mites. They had already undergone several topical and systemic treatments, including courses on oral corticosteroids. None of them had received systemic immunosuppressive agents, but they were refusing this type of treatment due to fear of the pandemic. All had a good response to dupilumab, evidenced by a reduction in the number of skin lesions and pruritus, with few side effects. Two patients had symptoms suggestive of COVID-19 during treatment with dupilumab (one confirmed by PCR) with a good outcome. In conclusion, patients with severe AD have a great impact on quality of life and, during the COVID-19 pandemic, many had a significant worsening of their dermatological condition. In this context, dupilumab proved to be an effective and safe therapeutic option for the treatment of these patients.


Subject(s)
Humans , Adolescent , Young Adult , Dermatitis, Atopic , Antibodies, Monoclonal, Humanized , COVID-19 , Patients , Pruritus , Quality of Life , Asthma , Signs and Symptoms , Azathioprine , Therapeutics , Biological Products , Immunoglobulin E , Interleukin-4 , Interleukin-13 , Rhinitis, Allergic , Mites
6.
Chinese Journal of Contemporary Pediatrics ; (12): 1044-1049, 2021.
Article in English | WPRIM | ID: wpr-922389

ABSTRACT

OBJECTIVES@#To study the expression levels of microRNA-138 (miR-138) and Runt-related transcription factor 3 (RUNX3) in peripheral blood of children with cough variant asthma (CVA) and their regulatory effects on Th1/Th2 balance.@*METHODS@#Sixty-five children with CVA (CVA group) and 30 healthy children (control group) were enrolled. Peripheral venous blood samples were collected for both groups, and CD4@*RESULTS@#Compared with the control group, the CVA group showed significantly decreased levels of IFN-γ and IL-2 from CD4@*CONCLUSIONS@#MiR-138 regulates Th1/Th2 balance by targeting RUNX3 in children with CVA, providing a new direction for the treatment of CVA.


Subject(s)
Child , Humans , Asthma , Core Binding Factor Alpha 3 Subunit/genetics , Cough , Interleukin-13 , MicroRNAs/genetics , Th1 Cells , Th1-Th2 Balance , Th2 Cells
7.
Journal of Southern Medical University ; (12): 1432-1438, 2020.
Article in Chinese | WPRIM | ID: wpr-880766

ABSTRACT

OBJECTIVE@#To investigate the effect of interleukin (IL) -13 combined with cold stimulation on synthesis and secretion of mucin (MUC) 5AC in human bronchial epithelial cell line 16HBE and explore the role of transient receptor potential 8 (TRPM8) and anti-apoptotic factor B-cell lymphoblast-2 (Bcl-2) in this process.@*METHODS@#16HBE cells were stimulated with 10 ng/mL IL-13, 1 mmol/L menthol, or both (1 mmol/L menthol was added after 6 days of IL-13 stimulation), and the changes in the expression of MUC5AC, intracellular Ca@*RESULTS@#The mRNA and protein expressions of MUC5AC increased significantly in 16HBE cells following stimulation with IL-13, menthol, and both (@*CONCLUSIONS@#Menthol combined with IL-13 produces a synergistic effect to promote the synthesis and secretion of MUC5AC in 16HBE cells possibly by activating TRPM8 receptor to upregulate the expression of Bcl-2.


Subject(s)
Humans , Bronchi , Epithelial Cells/drug effects , Interleukin-13 , Menthol/pharmacology , Mucin 5AC
8.
Allergy, Asthma & Immunology Research ; : 306-321, 2020.
Article in English | WPRIM | ID: wpr-785339

ABSTRACT

PURPOSE: Osteitis refers to the development of new bone formation and remodeling of bone in chronic rhinosinusitis (CRS) patients; it is typically associated with eosinophilia, nasal polyps (NPs), and recalcitrant CRS. However, the roles of ossification in CRS with or without NPs remain unclear due to the lack of appropriate animal models. Thus, it is necessary to have a suitable animal model for greater advances in the understanding of CRS pathogenesis.METHODS: BALB/c mice were administered ovalbumin (OVA) and staphylococcal enterotoxin B (SEB). The numbers of osteoclasts and osteoblasts and bony changes were assessed. Micro computed tomography (micro-CT) scans were conducted to measure bone thickness. Immunofluorescence, immunohistochemistry, and quantitative polymerase chain reaction were performed to evaluate runt-related transcription factor 2 (RUNX2), osteonectin, interleukin (IL)-13, and RUNX2 downstream gene expression. Gene set enrichment analysis was performed in mucosal tissues from control and CRS patients. The effect of resveratrol was evaluated in terms of osteogenesis in a murine eosinophilic CRS NP model.RESULTS: The histopathologic changes showed markedly thickened bones with significant increase in osteoblast numbers in OVA/SEB-treated mice compared to the phosphate-buffered saline-treated mice. The structural changes in bone on micro-CT were consistent with the histopathological features. The expression of RUNX2 and IL-13 was increased by the administration of OVA/SEB and showed a positive correlation. RUNX2 expression mainly co-localized with osteoblasts. Bioinformatic analysis using human CRS transcriptome revealed that IL-13-induced bony changes via RUNX2. Treatment with resveratrol, a candidate drug against osteitis, diminished the expression of IL-13 and RUNX2, and the number of osteoblasts in OVA/SEB-treated mice.CONCLUSIONS: In the present study, we found the histopathological and radiographic evidence of osteogenesis using a previously established murine eosinophilic CRS NP model. This animal model could provide new insights into the pathophysiology of neo-osteogenesis and provide a basis for developing new therapeutics.


Subject(s)
Animals , Humans , Mice , Computational Biology , Core Binding Factor Alpha 1 Subunit , Enterotoxins , Eosinophilia , Eosinophils , Fluorescent Antibody Technique , Gene Expression , Immunohistochemistry , Interleukin-13 , Interleukins , Models, Animal , Mucous Membrane , Nasal Polyps , Nose , Osteitis , Osteoblasts , Osteoclasts , Osteogenesis , Osteonectin , Ovalbumin , Polymerase Chain Reaction , Sinusitis , Transcription Factors , Transcriptome
9.
Allergy, Asthma & Immunology Research ; : 412-429, 2020.
Article in English | WPRIM | ID: wpr-811069

ABSTRACT

PURPOSE: Different characteristics of airway microbiome in asthmatics may lead to differential immune responses, which in turn cause eosinophilic or neutrophilic airway inflammation. However, the relationships among these factors have yet to be fully elucidated.METHODS: Microbes in induced sputum samples were subjected to sequence analysis of 16S rRNA. Airway inflammatory phenotypes were defined as neutrophils (>60%) and eosinophils (>3%), and inflammation endotypes were defined by levels of T helper (Th) 1 (interferon-γ), Th2 (interleukin [IL]-5 and IL-13), Th-17 (IL-17), and innate Th2 (IL-25, IL-33, and thymic stromal lymphopoietin) cytokines, inflammasomes (IL-1β), epithelial activation markers (granulocyte-macrophage colony-stimulating factor and IL-8), and Inflammation (IL-6 and tumor necrosis factor-α) cytokines in sputum supernatants was assessed by enzyme-linked immunosorbent assay.RESULTS: The numbers of operational taxonomic units were significantly higher in the mixed (n = 21) and neutrophilic (n = 23) inflammation groups than in the paucigranulocytic inflammation group (n = 19; p < 0.05). At the species level, Granulicatella adiacens, Streptococcus parasanguinis, Streptococcus pneumoniae, Veillonella rogosae, Haemophilus parainfluenzae, and Neisseria perflava levels were significantly higher in the eosinophilic inflammation group (n = 20), whereas JYGU_s levels were significantly higher in the neutrophilic inflammation group compared to the other subtypes (P < 0.05). Additionally, IL-5 and IL-13 concentrations were correlated with the percentage of eosinophils (P < 0.05) and IL-13 levels were positively correlated with the read counts of Porphyromonas pasteri and V. rogosae (P < 0.05). IL-1β concentrations were correlated with the percentage of neutrophils (P < 0.05). had a tendency to be positively correlated with the read count of JYGU_s (P = 0.095), and was negatively correlated with that of S. pneumoniae (P < 0.05).CONCLUSIONS: Difference of microbial patterns in airways may induce distinctive endotypes of asthma, which is responsible for the neutrophilic or eosinophilic inflammation in asthma.


Subject(s)
Asthma , Colony-Stimulating Factors , Cytokines , Enzyme-Linked Immunosorbent Assay , Eosinophils , Haemophilus parainfluenzae , Inflammasomes , Inflammation , Interleukin-13 , Interleukin-33 , Interleukin-5 , Microbiota , Necrosis , Neisseria , Neutrophils , Phenotype , Pneumonia , Porphyromonas , Sequence Analysis , Sputum , Streptococcus , Streptococcus pneumoniae , Veillonella
10.
Allergy, Asthma & Immunology Research ; : 537-555, 2020.
Article in English | WPRIM | ID: wpr-811060

ABSTRACT

PURPOSE: Simple and reliable animal models of human diseases contribute to the understanding of disease pathogenesis as well as the development of therapeutic interventions. Although several murine models to mimic human asthma have been established, most of them require anesthesia, resulting in variability among test individuals, and do not mimic asthmatic responses accompanied by T-helper (Th) 17 and neutrophils. As dendritic cells (DCs) are known to play an important role in initiating and maintaining asthmatic inflammation, we developed an asthma model via adoptive transfer of allergen-loaded DCs.METHODS: Ovalbumin (OVA)-loaded bone marrow-derived DCs (BMDCs) (OVA-BMDCs) were injected intravenously 3 times into non-anesthetized C57BL/6 mice after intraperitoneal OVA-sensitization.RESULTS: OVA-BMDC-transferred mice developed severe asthmatic immune responses when compared with mice receiving conventional OVA challenge intranasally. Notably, remarkable increases in systemic immunoglobulin (Ig) E and IgG1 responses, Th2/Th17-associated cytokines (interleukin [IL]-5, IL-13 and IL-17), Th2/Th17-skewed T-cell responses, and cellular components, including eosinophils, neutrophils, and goblet cells, were observed in the lungs of OVA-BMDC-transferred mice. Moreover, the asthmatic immune responses and severity of inflammation were correlated with the number of OVA-BMDCs transferred, indicating that the disease severity and asthma type may be adjusted according to the experimental purpose by this method. Furthermore, this model exhibited less variation among the test individuals than the conventional model. In addition, this DCs-based asthma model was partially resistant to steroid treatment.CONCLUSIONS: A reliable murine model of asthma by intravenous (i.v.) transfer of OVA-BMDCs was successfully established without anesthesia. This model more accurately reflects heterogeneous human asthma, exhibiting a robust Th2/Th17-skewed response and eosinophilic/neutrophilic infiltration with good reproducibility and low variation among individuals. This model will be useful for understanding the pathogenesis of asthma and would serve as an alternative tool for immunological studies on the function of DCs, T-cell responses and new drugs.


Subject(s)
Animals , Humans , Mice , Adoptive Transfer , Anesthesia , Asthma , Cytokines , Dendritic Cells , Eosinophils , Goblet Cells , Immunoglobulin G , Immunoglobulins , Inflammation , Interleukin-13 , Lung , Methods , Models, Animal , Neutrophils , Ovalbumin , Ovum , T-Lymphocytes
11.
Arq. Asma, Alerg. Imunol ; 3(3): 283-290, jul.set.2019. ilus
Article in Portuguese | LILACS | ID: biblio-1381270

ABSTRACT

Introdução: A asma é uma doença complexa, resultante da interação entre fatores genéticos e ambientais. A expressão aumentada de genes relacionados à inflamação define as alterações celulares e estruturais do aparelho respiratório, enquanto o meio ambiente modula os diferentes fenótipos asmáticos. Os produtos dessas células envolvidos na inflamação incluem citocinas, como a interleucina13 (IL-13), que está relacionada com a síntese direta de IgE, imunoglobulina essencial na patogênese da asma. Há divergências entre a prevalência da asma e o grupo étnico estudado, desta forma, o uso de Marcadores Informativos de Ancestralidade (AIM ­ Ancestry Informative Markers) possibilita a caracterização da ancestralidade genômica de diferentes populações. Objetivos: Verificar a associação entre polimorfismos do gene IL-13R com a ancestralidade genômica e a asma em uma população no sul da Bahia. Métodos: Foram genotipadas 320 amostras, sendo 114 casos, e 206 controles, utilizando o método de PCR e PCR/RFLP em sete AIMs (Sb19.3, APO, AT3, RB2300, LPL, CKMM e PV92) que apresentam elevado diferencial de frequência alélica entre africanos, ameríndios e europeu, e um polimorfismo no receptor de IL-13 (IL-13RA1). Resultados: Os resultados desse estudo mostraram que a maior contribuição foi ameríndia, tanto para os casos (37,42%), como para os controles (50,52%), demonstrando que há diferenças nas contribuições étnicas das amostras da região estudada. O polimorfismo no receptor de IL-13 (IL- 13RA1) apresentou associação significativa com rinite e história familiar. Conclusões: A heterogeneidade da composição étnica das amostras pode ter influenciado na não associação das duas variáveis: níveis de IgE sérico e histórico familiar, e a presença do polimorfismo no receptor da IL-13RA1, e aponta a necessidade de realização do controle genômico.


Introduction: Asthma is a complex disease resulting from the interaction between genetic and environmental factors. Increased expression of inflammatory genes defines cellular and structural changes in the respiratory tract, while the environment modulates the different asthmatic phenotypes. Cell products involved in inflammation include cytokines, such as interleukin-13 (IL-13), which is related to the direct synthesis of IgE, an immunoglobulin that plays a key role in the pathogenesis of asthma. Because there is divergence of asthma prevalence between different ethnic groups, the use of ancestry informative markers (AIMs) allows for the characterization of genomic ancestry in different populations. Objectives: To examine the association of IL-13R gene polymorphisms with genomic ancestry and asthma in a population from the south of Bahia. Methods: A total of 320 samples, 114 cases and 206 controls, were genotyped using PCR and PCR/RFLP methods for 7 AIMs (Sb19.3, APO, AT3, RB2300, LPL, CKMM, and PV92) that showed a high allele frequency differential between Africans, Amerindians, and Europeans and 1 polymorphism in the IL-13 receptor (IL-13RA1). Results: Amerindian ancestry provided the greatest contribution in both cases (37.42%) and controls (50.52%), indicating that there are differences in the ethnic contribution of the samples from the study region. The IL-13 receptor (IL-13RA1) polymorphism was significantly associated with rhinitis and family history. Conclusions: Heterogeneity in the ethnic composition of the samples may have influenced the non-association of serum IgE levels and family history with the presence of IL-13RA1 receptor polymorphism, and the results point to the need for genomic control.


Subject(s)
Humans , Asthma , Immunoglobulin E , Interleukin-13 , Genomics , Receptors, Interleukin-13 , Phenotype , Polymorphism, Genetic , Respiratory System , Ethnicity , Polymerase Chain Reaction , Prevalence , American Indian or Alaska Native , Methods
12.
Allergy, Asthma & Immunology Research ; : 267-279, 2019.
Article in English | WPRIM | ID: wpr-739395

ABSTRACT

PURPOSE: Vitamin D is a potent immunomodulator. However, its role in the pathogenesis of allergic rhinitis is unclear. METHODS: The aim of this study was to evaluate the antiallergic effect of intranasally applied vitamin D in an allergic rhinitis mouse model. BALB/c mice were intraperitoneally sensitized with ovalbumin (OVA) and alum before they were intranasally challenged with OVA. Then, they were intranasally administered 1, 25-dihydroxyvitamin D3 (0.02 μg) or solvent. Allergic symptom scores, eosinophil infiltration, cytokine mRNA levels (interleukin [IL]-4, IL-5, IL-10, IL-13 and interferon-γ) in the nasal tissue, and serum total immunoglobulin E (IgE) and OVA-specific IgE, IgG1, and IgG2a were analyzed and compared with negative and positive control groups. Cervical lymph nodes (LNs) were harvested for flow cytometry analysis and cell proliferation assay. RESULTS: In the treatment group, allergic symptom scores, eosinophil infiltration, and mRNA levels of IL-4 and IL-13 were significantly lower in the nasal tissue than in the positive control group. The IL-5 mRNA level, serum total IgE, and OVA-specific IgE and IgG1 levels decreased in the treatment group; however, the difference was not significant. In the cervical LNs, CD86 expression had been down-regulated in CD11c+major histocompatibility complex II-high (MHCIIhigh) in the treatment group. Additionally, IL-4 secretion in the lymphocyte culture from cervical LNs significantly decreased. CONCLUSIONS: The results confirm the antiallergic effect of intranasal 1,25-dihydroxyvitamin D3. It decreases CD 86 expression among CD11c+MHCIIhigh cells and T-helper type 2-mediated inflammation in the cervical LNs. Therefore, topically applied 1,25-dihydroxyvitamin D3 can be a future therapeutic agent for allergic rhinitis.


Subject(s)
Animals , Mice , Administration, Intranasal , Anti-Allergic Agents , Calcitriol , Cell Proliferation , Dendritic Cells , Eosinophils , Flow Cytometry , Immunoglobulin E , Immunoglobulin G , Immunoglobulins , Inflammation , Interleukin-10 , Interleukin-13 , Interleukin-4 , Interleukin-5 , Lymph Nodes , Lymphocytes , Major Histocompatibility Complex , Models, Animal , Ovalbumin , Ovum , Rhinitis, Allergic , RNA, Messenger , Vitamin D
13.
Chinese Journal of Contemporary Pediatrics ; (12): 861-867, 2019.
Article in Chinese | WPRIM | ID: wpr-775092

ABSTRACT

OBJECTIVE@#To examine the levels of airway inflammatory mediators in peripheral blood in infants and young children with wheezing and to study the possible pathogenesis of wheezing from the aspects of T helper cell 1 (Th1)/T helper cell 2 (Th2) imbalance and airway inflammation.@*METHODS@#A total of 50 children aged 1 month to 3 years with an acute wheezing episode were enrolled as the wheezing group, and 25 age-matched healthy infants were enrolled as the healthy control group. According to the number of wheezing episodes, the wheezing group was divided into a first-episode group (n=25) and a recurrent wheezing (number of episodes ≥2) group (n=25). According to the presence or absence of high-risk factors for asthma, the wheezing group was divided into a high-risk factor group (n=22) and a non-high-risk factor group (n=28). According to the results of pathogen detection, the wheezing group was divided into a positive pathogen group (n=23) and a negative pathogen group (n=27). Levels of interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-13 (IL-13), transforming growth factor-β1 (TGF-β1), and total IgE (TIgE) in peripheral blood were measured for each group. For children with wheezing, eosinophil (EOS) count in peripheral blood was measured, and related samples were collected for respiratory pathogen detection.@*RESULTS@#The wheezing group had significantly higher levels of IL-4, IL-5, IL-13, TGF-β1, and TIgE in peripheral blood than the healthy control group (P0.05). The correlation analysis showed that in children with wheezing, EOS count was positively correlated with IL-4 level (P<0.01), IL-4 level was positively correlated with IL-5 and IL-13 levels (P<0.01), IL-5 level was positively correlated with IL-13 level (P<0.01), and IL-2 level was positively correlated with TGF-β1 level (P<0.05).@*CONCLUSIONS@#Th1/Th2 imbalance with a predominance of Th2 is observed in infants and young children with wheezing. IL-4, IL-5, IL-13, TGF-β1, and IgE are involved in the pathogenesis of wheezing in these children. Airway inflammation is also observed in these children with wheezing, but it is not associated with the number of wheezing episodes, presence or absence of high-risk factors for asthma, or results of pathogen detection.


Subject(s)
Child , Child, Preschool , Humans , Infant , Asthma , Inflammation Mediators , Interleukin-13 , Respiratory Sounds , Th1 Cells
14.
Tuberculosis and Respiratory Diseases ; : 71-80, 2019.
Article in English | WPRIM | ID: wpr-719615

ABSTRACT

BACKGROUND: Efficacy and safety of tiotropium bromide, a muscarinic receptor antagonist, in treatment of asthma have been reported. However, its effect on airway remodeling in chronic asthma of the elderly has not been clearly verified. The objective of this study was to investigate the effect of tiotropium and expression of muscarinic receptors as its related mechanism in an aged mouse model of chronic asthma with airway remodeling. METHODS: BALB/c female mice age 6 weeks, 9 and 15 months were sensitized and challenged with ovalbumin (OVA) for three months. Tiotropium bromide was administered during the challenge period. Airway hyperresponsiveness (AHR) and pulmonary inflammation were measured. Parameters of airway remodeling, and expression levels of M2 and M3 receptors were examined. RESULTS: Total cell with eosinophils, increased in the OVA groups by age, was decreased significantly after treatment with tiotropium bromide, particularly in the age group of 15 months. AHR and levels of interleukin (IL)-4, IL-5, and IL-13 were decreased, after tiotropium administration. In old aged group of 9- and 15-months-treated groups, hydroxyproline contents and levels of α-smooth muscle actin were attenuated. Tiotropium enhanced the expression of M2 but decreased expression of M3 in all aged groups of OVA. CONCLUSION: Tiotropium bromide had anti-inflammatory and anti-remodeling effects in an aged mouse model of chronic asthma. Its effects seemed to be partly mediated by modulating expression M3 and M2 muscarinic receptors. Tiotropium may be a beneficial treatment option for the elderly with airway remodeling of chronic asthma.


Subject(s)
Aged , Animals , Female , Humans , Mice , Actins , Airway Remodeling , Asthma , Eosinophils , Hydroxyproline , Interleukin-13 , Interleukin-5 , Interleukins , Ovalbumin , Ovum , Pneumonia , Receptors, Muscarinic , Tiotropium Bromide
15.
Psychiatry Investigation ; : 607-614, 2019.
Article in English | WPRIM | ID: wpr-760969

ABSTRACT

OBJECTIVE: Since the inflammatory process has been implicated in the pathophysiology of psychiatric disorder, an important issue emerging is to assess the test-retest reliability of cytokine measurement in healthy individuals and patients with schizophrenia. The objective of the present study was to investigate the test-retest reliability of bead-based multiplex immunoassay technology (BMIT) for cytokine measurement by using a Bland-Altman plot (BAP). METHODS: Twenty healthy individuals and twenty patients with schizophrenia were enrolled, and a 17-plex cytokine assay was used to measure inflammatory biomarkers at baseline and two weeks later. The test-retest reliability was examined by BAP, 95% limits of agreement (LOA), intraclass correlation coefficient (ICC), and coefficient of repeatability (CoR). RESULTS: In the healthy controls, only interleukin (IL)-2, IL-13, IL-10, IL-17, and macrophage inflammatory protein-1β showed excellent ICC. The BAP with 95% LOA determined that 13 cytokines showed acceptable 95% LOA for a 2-week test-retest reliability, and only IL-1β, IL-12 and tumor necrosis factor (TNF)-α had significant test-retest bias. The CoR of cytokines varied significantly, ranging from 1.72 to 218.1. Compared with healthy controls, patients with schizophrenia showed significantly higher levels of IL-5, IL-13, and TNF-α and significantly lower levels of IL-4, IL-12, and interferon-gamma (IFN-γ). Of these six cytokines, IL-12 and TNF-α were considered suboptimal reliability. CONCLUSION: The findings from ICC and CoR implied that the test-retest reliability of BMIT for cytokine measurement were suboptimal. However, the BAP with 95% LOA confirmed that BMIT can reliably distinguish schizophrenia from healthy individuals in cytokine measurement, while significant within-subject variation and between-group overlapping were evident in cytokine expression.


Subject(s)
Humans , Bias , Biomarkers , Cytokines , Immunoassay , Inflammation , Interferon-gamma , Interleukin-10 , Interleukin-12 , Interleukin-13 , Interleukin-17 , Interleukin-4 , Interleukin-5 , Interleukins , Loa , Macrophages , Reproducibility of Results , Schizophrenia , Tumor Necrosis Factor-alpha
16.
Clinical and Experimental Otorhinolaryngology ; : 196-205, 2019.
Article in English | WPRIM | ID: wpr-763299

ABSTRACT

OBJECTIVES: The extract of Hizikia fusiformis is known to exhibit anticancer, antiatopic and antioxidant activities. We aimed to investigate the extract of H. fusiformis on allergic rhinitis inflammation in a mouse model. METHODS: The 4-week-old BALB/c mice were randomly assigned into four groups: group A, control group (n=9); group B, allergic rhinitis group (n=10); group C (n=10) received 300 mg/kg of H. fusiformis during nasal challenging period; group D (n=10) received 600 mg/kg of H. fusiformis during general sensitization period and 300 mg/kg of H. fusiformis during nasal challenging period. Allergic inflammation was made with ovalbumin (OVA) and alum then challenged intranasally with OVA. H. fusiformis was intraperitoneally administered 3 hours before the OVA administration. Allergic symptom score and the levels of immunoglobulin G1 (IgG1), IgG2a, OVA-specific IgE antibodies, levels of cytokines in the nasal mucosa and in spleen cell culture supernatant, such as tumor necrosis factor alpha (TNF-α), interleukin 4 (IL-4), IL-5, IL-13, and IL-10 were assessed. The percentage of regulatory T cell was analyzed by flow cytometry. Eosinophilic infiltration and goblet cell hyperplasia were also evaluated. RESULTS: H. fusiformis administered groups C and D showed significant inhibitory effects on nasal symptoms, IL-13 mRNA expression and eosinophil infiltration/goblet cell hyperplasia in the nasal tissue; OVA-specific IgE production in serum (P<0.05). In group D, H. fusiformis treatment downregulated IL-4, IL-5, IL-13, TNF-α, and IL-10 cytokine expression in splenocyte culture as well as significantly decreased IgG2a, IgG1 levels in serum compared with group B (P<0.05). However, the expressions of IL-5, interferon-γ and forkhead box P3 mRNA did not change in groups C and D. CONCLUSION: H. fusiformis could induce antiallergic inflammation by suppressing the T-helper type 2 cytokine production (IL-13) locally and systemically, OVA-specific IgE formation, goblet cell hyperplasia, and eosinophilic infiltration in a mouse model of allergic rhinitis. Thus, H. fusiformis could be considered as a potential therapeutic agent in treating allergic rhinitis.


Subject(s)
Animals , Mice , Antibodies , Cell Culture Techniques , Cytokines , Eosinophils , Flow Cytometry , Goblet Cells , Hyperplasia , Immunoglobulin E , Immunoglobulin G , Immunoglobulins , Inflammation , Interleukin-10 , Interleukin-13 , Interleukin-4 , Interleukin-5 , Nasal Mucosa , Ovalbumin , Ovum , Rhinitis, Allergic , RNA, Messenger , Spleen , Th2 Cells , Tumor Necrosis Factor-alpha
17.
Immune Network ; : 42-2019.
Article in English | WPRIM | ID: wpr-785819

ABSTRACT

There have been few studies investigating the association between atopic dermatitis (AD) and prenatal exposure to heavy metals. We aimed to evaluate whether prenatal exposure to heavy metals is associated with the development or severity of AD in a birth cohort study. A total of 331 subjects were followed from birth for a median duration of 60.0 months. The presence and severity of AD were evaluated at ages 6 and 12 months, and regularly once a year thereafter. The concentrations of lead, mercury, chromium, and cadmium in umbilical cord blood were measured by inductively coupled plasma mass spectrometry. Cord blood mononuclear cells (CBMCs) were isolated and stimulated for analysis of cytokine production using ELISA. Heavy metal levels in cord blood were not associated with the development of AD until 24 months of age. However, a positive correlation was observed between the duration of AD and lead levels in cord blood (p=0.002). AD severity was also positively associated with chromium concentrations in cord blood (p=0.037), while cord blood levels of lead, mercury, and cadmium were not significantly associated with AD severity (p=0.562, p=0.054, and p=0.055, respectively). Interleukin-13 production in CBMCs was positively related with lead and chromium levels in cord blood (p=0.021 and p=0.015, respectively). Prenatal exposure to lead and chromium is associated with the persistence and severity of AD, and the immune reaction toward a Th2 polarization.


Subject(s)
Cacao , Cadmium , Chromium , Cohort Studies , Dermatitis, Atopic , Enzyme-Linked Immunosorbent Assay , Fetal Blood , Interleukin-13 , Mass Spectrometry , Metals, Heavy , Parturition , Plasma , Umbilical Cord
18.
Annals of Dermatology ; : 538-544, 2019.
Article in English | WPRIM | ID: wpr-762375

ABSTRACT

BACKGROUND: Recent studies have reported that glucosamine (GlcN) showed therapeutic effects in allergic diseases such as asthma and rhinitis, and its mechanisms include the suppression of T helper type 2 immune responses and the nuclear factor-κB pathway. OBJECTIVE: We aimed to investigate the effect of GlcN on atopic dermatitis (AD) in an animal model. METHODS: Twenty-five BALB/c mice were divided into five groups (groups A~E). Group A was the phosphate-buffered saline (PBS)-treated group without AD induction. Group B was the PBS control group with AD induction. Groups C to E were the AD induction groups, which were treated with three different doses of GlcN (10 mg, 20 mg, and 40 mg, respectively). Histopathological examination was performed after GlcN administration. Interleukin (IL)-4, IL-13, and IL-17 cytokine levels were measured by enzyme-linked immunosorbent assay using skin biopsy specimens. Serum total immunoglobulin E (IgE) concentrations were measured before and after administration with GlcN or PBS. RESULTS: Clinical dermatitis scores decreased with increasing GlcN dose (p<0.001). Concentrations of tissue IL-13 and IL-17 decreased after GlcN administration (each group: p=0.002 and p<0.001, respectively), but the concentrations of tissue IL-4 did not show differences across groups. Serum IgE levels tended to be lower after GlcN administration (p=0.004). Histopathological scores were not significantly different among groups B~E (p=0.394). CONCLUSION: GlcN improved AD symptoms and decreased tissue IL-13, IL-17, and serum total IgE levels in an animal model.


Subject(s)
Animals , Mice , Allergy and Immunology , Anti-Allergic Agents , Asthma , Biopsy , Dermatitis , Dermatitis, Atopic , Enzyme-Linked Immunosorbent Assay , Glucosamine , Immunoglobulin E , Immunoglobulins , Interleukin-13 , Interleukin-17 , Interleukin-4 , Interleukins , Models, Animal , Rhinitis , Skin , Therapeutic Uses
19.
Allergy, Asthma & Immunology Research ; : 604-621, 2019.
Article in English | WPRIM | ID: wpr-762160

ABSTRACT

Asthma is a common disorder of the airways characterized by airway inflammation and by decline in lung function and airway remodeling in a subset of asthmatics. Airway remodeling is characterized by structural changes which include airway smooth muscle hypertrophy/hyperplasia, subepithelial fibrosis due to thickening of the reticular basement membrane, mucus metaplasia of the epithelium, and angiogenesis. Epidemiologic studies suggest that both genetic and environmental factors may contribute to decline in lung function and airway remodeling in a subset of asthmatics. Environmental factors include respiratory viral infection-triggered asthma exacerbations, and tobacco smoke. There is also evidence that several asthma candidate genes may contribute to decline in lung function, including ADAM33, PLAUR, VEGF, IL13, CHI3L1, TSLP, GSDMB, TGFB1, POSTN, ESR1 and ARG2. In addition, mediators or cytokines, including cysteinyl leukotrienes, matrix metallopeptidase-9, interleukin-33 and eosinophil expression of transforming growth factor-β, may contribute to airway remodeling in asthma. Although increased airway smooth muscle is associated with reduced lung function (i.e. forced expiratory volume in 1 second) in asthma, there have been few long-term studies to determine how individual pathologic features of airway remodeling contribute to decline in lung function in asthma. Clinical studies with inhibitors of individual gene products, cytokines or mediators are needed in asthmatic patients to identify their individual role in decline in lung function and/or airway remodeling.


Subject(s)
Humans , Airway Remodeling , Asthma , Basement Membrane , Cytokines , Eosinophils , Epidemiologic Studies , Epithelium , Fibrosis , Forced Expiratory Volume , Inflammation , Interleukin-13 , Interleukin-33 , Leukotrienes , Lung , Metaplasia , Mucus , Muscle, Smooth , Respiratory Function Tests , Smoke , Nicotiana , Vascular Endothelial Growth Factor A
20.
The Korean Journal of Parasitology ; : 225-232, 2019.
Article in English | WPRIM | ID: wpr-761748

ABSTRACT

Innate lymphoid cells (ILCs) are key players during an immune response at the mucosal surfaces, such as lung, skin, and gastrointestinal tract. Giardia lamblia is an extracellular protozoan pathogen that inhabits the human small intestine. In this study, ILCs prepared from the lamina propria of mouse small intestine were incubated with G. lamblia trophozoites. Transcriptional changes in G. lamblia-exposed ILCs resulted in identification of activation of several immune pathways. Secretion of interleukin (IL)-17A, IL-17F, IL-1β, and interferon-γ was increased, whereas levels of IL-13, IL-5, and IL-22, was maintained or reduced upon exposure to G. lamblia. Goup 3 ILC (ILC3) was found to be dominant amongst the ILCs, and increased significantly upon co-cultivation with G. lamblia trophozoites. Oral inoculation of G. lamblia trophozoites into mice resulted in their presence in the small intestine, of which, the highest number of parasites was detected at the 5 days-post infection. Increased ILC3 was observed amongst the ILC population at the 5 days-post infection. These findings indicate that ILC3 from the lamina propria secretes IL-17 in response to G. lamblia, leading to the intestinal pathology observed in giardiasis.


Subject(s)
Animals , Humans , Mice , Gastrointestinal Tract , Giardia lamblia , Giardia , Giardiasis , Interleukin-13 , Interleukin-17 , Interleukin-5 , Interleukins , Intestine, Small , Lung , Lymphocytes , Mucous Membrane , Parasites , Pathology , Skin , Trophozoites
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