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2.
An. bras. dermatol ; 96(5): 551-557, Sept.-Oct. 2021. tab
Article in English | LILACS | ID: biblio-1345130

ABSTRACT

Abstract Background: Alopecia areata (AA) is a hair disease that causes hair loss without scarring. The etiopathogenesis of AA has not been fully understood yet. Objective: To determine serum interleukin levels (IL-2, IL-4, IL-15, and IL-17) in patients diagnosed with alopecia areata and to investigate the relationship of IL levels with the duration and severity of alopecia areata and the response to tofacitinib therapy. Methods: Patients (≥16 years old) diagnosed with alopecia areata and healthy individuals as a control group was enrolled. Baseline serum interleukin levels of the patients and controls were measured. In the patient group receiving tofacitinib therapy, serum interleukin levels were measured again after 6 months. Disease severity for alopecia areata was assessed using the Severity of Alopecia Tool. Results: Sixty-one AA patients and 30 healthy individuals were included; they were comparable regarding age and sex. The mean disease duration for AA was 7 ± 6 years and the baseline mean Severity of Alopecia Tool score was 71 ± 30 (range, 20-100). Baseline IL-2, IL-4 and IL-15 levels were significantly higher in the patient group than those in the control group (p < 0.001 for each). No significant correlation was found between the baseline interleukin levels and either disease duration or disease severity (baseline Severity of Alopecia Tool score). Among the patients receiving tofacitinib (n = 22), all interleukin levels significantly decreased after treatment. However, no significant relationship between the change in interleukin levels and the change in the Severity of Alopecia Tool scores was observed after tofacitinib treatment. Study limitations: This is a monocentric study conducted in a single university hospital. Conclusion: High interleukin levels in alopecia areata patients and the significant decrease with treatment support the idea that interleukins have a role in pathogenesis. Nevertheless, no relationship could be demonstrated between IL levels and disease duration or severity.


Subject(s)
Humans , Adolescent , Interleukin-2 , Alopecia Areata/drug therapy , Severity of Illness Index , Interleukins , Interleukin-4 , Interleukin-15 , Interleukin-17
3.
Rev. bras. geriatr. gerontol. (Online) ; 24(2): e200350, 2021. tab, graf
Article in English, Portuguese | LILACS | ID: biblio-1288543

ABSTRACT

Resumo Objetivo investigar a associação entre a frequência de eventos estressores e citocinas em pessoas idosas longevas. Métodos os participantes responderam a um questionário constituído de variáveis sociodemográficas, indicaram quais eventos estressores constantes no Inventário de Eventos Estressores de vida ocorreram nos últimos cinco anos e responderam a escala de depressão geriátrica (GDS). Foram dosados por citometria de fluxo: interleucina (IL) 10, IL-6, IL-4, IL-2, fator de necrose tumoral (TNF-α) e interferon gama (IFN-γ). A análise descritiva foi realizada para a caracterização da amostra. Para investigar a associação entre as variáveis foi desenvolvido um modelo de regressão linear múltipla, utilizando o método Backward. Resultados Participaram da pesquisa 91 pessoas idosas com média de idade de 82 anos. Mais da metade da amostra relatou morte de ente querido como o evento estressor mais prevalente (61%). Nessa amostra foi possível perceber que quanto mais eventos estressores foram relatados, menor o nível de IL-4 (p=0,046), da mesma forma que o estado civil viuvez, onde os dados mostraram que quem é viúvo tem menos eventos estressores em comparação a quem é casado (p=0,037). Conclusão Evidenciou-se a importância de um olhar mais cuidadoso dos profissionais de saúde na avaliação multidimensional da pessoa idosa, de forma que se obtenham subsídios para a implementação de programas e intervenções específicos que possam amenizar a percepção dos eventos estressores vivenciados, colaborando com menores danos decorrentes da imunossenescência.


Abstract Objective To investigate the association between the frequency of stressor events and cytokines in long-lived older people. Methods The participants answered a questionnaire consisting of sociodemographic variables, indicated which stressor events included in the Stressor Life Events Inventory occurred in the last five years and answered the Geriatric Depression Scale (GDS). The following were measured by flow cytometry: interleukin (IL) 10, IL-6, IL-4, IL-2, tumor necrosis factor (TNF-α) and interferon gamma (IFN-γ). We carried out a descriptive statistical analysis in order to characterize the sample. To investigate the association between the variables, a multiple linear regression model was developed, using the Backward method. Results 91 older people with an age average of 82 years participated in the research. More than half of the sample reported the death of a loved one as the most prevalent stressor event (61%). In this sample, it was possible to notice that the more stressor events were reported, the lower the level of IL-4 (p=0.046), as well as the marital status of widowhood, where data showed that those who are widowed have fewer stressor events in comparison to who is married (p=0.037). Conclusion The importance of a more careful look by health professionals in older people multidimensional assessment was evidenced, so that subsidies are obtained for the implementation of specific programs and interventions that can ease the perception of the stressor events experienced, collaborating with less resulting damage of immunosenescence.


Subject(s)
Humans , Male , Female , Aged, 80 and over , Aged , Health of the Elderly , Cytokines , Interleukin-4 , Psychological Distress
4.
Article in Chinese | WPRIM | ID: wpr-888019

ABSTRACT

To study the effect of anemoside B4 on rats with chronic obstructive pulmonary disease (COPD).Seventy-two SD male rats were randomly divided into blank group and model group.The method of exposure to cigarette smoke and combined with lipopolysaccharide (LPS) was used to replicate the rat model of COPD.After the model was maintained for 5 weeks,the rats were randomly divided into model group,dexamethasone group (0.81 mg·kg~(-1)) and anemoside B4 low,medium and high (2,4,8 mg·kg~(-1)) dose groups,a group of 12 animals were administered,and then the administration was started.The administration was maintained until the28th day,and the pulmonary function parameters of rats were measured by an animal pulmonary function instrument.After testing the rat lung function parameters,immediately draw rat alveolar lavage fluid (BALF),and use high-throughput protein chip technology to determined the expression levels of inflammatory cytokines in rat BALF.HE staining was used to observe the general pathological changes of rat lung and tracheal tissue.Masson staining was used to observe the collagen deposition in rat lung tissue.Real-time q PCR method was used to determine the mRNA expression level of related genes in rat lung tissue.Western blot method was used to determine the expression levels of related proteins in rat lung tissues.According to the findings,compared with the model group,the dexamethasone group and the anemoside B4 drug groups had different degrees of increase in the lung function parameters of rats (P<0.01,P<0.05),improved the expression level of inflammatory cytokines in the BALF of rats to varying degrees (P<0.01,P<0.05),and improved the pathological structure of rat lung tissue to varying degrees.Relative mRNA expressions of matrix metalloproteinase 2 (MMP-2),matrix metalloproteinase 12 (MMP-12),matrix metalloproteinase inhibitor 1 (TIMP-1),interleukin-6 (IL-6),and transforming growth factor-β1 (TGF-β1) were significantly reduced (P<0.01);whereas relative mRNA expressions of matrix metalloproteinase 9(MMP-9) and matrix metalloproteinase inhibitor 2 (TIMP-2) were increased significantly (P<0.01).The mRNA and protein expression levels of T-box transcription factor (T-bet),interleukin-12 (IL-12) and signal transducer and activator of transcription 4(STAT4) reduced to varying degrees (P<0.01,P<0.05).The mRNA of transcription factor GATA3 (binding protein-3),interleukin-4 (IL-4) and signal transducer and activator of transcription 6 (STAT6) in rat lung tissues and the protein expression levels of IL-4 and STAT6 were increased to varying degrees (P<0.01,P<0.05).In conclusion,anemoside B4 has a certain protective effect on COPD rats caused by cigarette smoke exposure and combined with LPS.The mechanism of action may be related to the regulation of IL-12/STAT4 and IL-4/STAT6 signaling pathways.


Subject(s)
Animals , Interleukin-12 , Interleukin-4 , Lung/metabolism , Male , Matrix Metalloproteinase 2 , Pulmonary Disease, Chronic Obstructive/genetics , Rats , STAT4 Transcription Factor/metabolism , STAT6 Transcription Factor/metabolism , Saponins
5.
Cienc. tecnol. salud ; 7(2): 236-250, 2020. il 27 c
Article in Spanish | LILACS, LIGCSA, DIGIUSAC | ID: biblio-1348233

ABSTRACT

El cáncer gástrico (CG) es un problema prevalente a nivel mundial, presentándose aproximadamente 18 millones de casos nuevos en el año 2018, representa el 5.7% del total de cánceres, siendo la quinta neoplasia maligna más común en el mundo. En Guatemala se sitúa entre los primeros cinco cánceres respecto a morbilidad y mor-talidad. El CG se ha asociado de manera contundente a infección por Helicobacter pylori el cual desencadena un proceso inflamatorio crónico; adicionalmente algunas cepas de H. pylori producen toxinas bacterianas capaces de inducir cambios celulares que conllevan al desarrollo del proceso neoplásico. La alta mortalidad por CG en parte, se relaciona con la etapa tardía en la que se diagnostica ya que se requiere el uso de métodos invasivos, lo que dificulta su detección temprana. El objetivo de la presente revisión, fue realizar una narrativa de los estudios y las evidencias científicas, respecto de la identificación de biomarcadores séricos en la detección temprana del cáncer gástrico. Se revisaron dos tipos de biomarcadores, la proteína soluble uPAR (suPAR) que es el receptor del activador del plasminógeno (uroquinasa) y promotora de angiogénesis y por otro lado, la detección sérica de las citocinas IL-1ß, IL-6, TNFα, IL-10, IFNγ, IL-4 e IL-17 en el CG así como su potencial utilidad en su detección temprana. Estos biomarcadores fueron seleccionados por la ventaja que tendrían de ser métodos no invasivos que podrían mejorar la detección, tratamiento y pronóstico de esta enfermedad.


Gastric cancer (GC) is a prevalent problem worldwide, presenting approximately 18 million new cases in 2018, representing 5.7% of all cancers, being the fifth most common malignancy in the world. In Guatemala it is among the first five cancers in terms of morbidity and mortality. CG has been strongly associated with Helicobacter pylori infection, which triggers a chronic inflammatory process; additionally, some strains of H. pylori produce bacterial toxins capable of inducing cellular changes that lead to the development of cancer. The high mortality due to GC in part is related to the late stage in which it is diagnosed since the use of invasive methods is required, making it difficult to detect it early. The objective of this review was to make a narrative of the studies carried out and the scientific evidence regarding the identification of serum biomarkers in the early detection of gastric cancer. Two types of biomarkers were reviewed, the soluble protein uPAR (suPAR) which is the receptor for plasminogen activator (urokinase) and promoter of angiogenesis and, on the other hand, serum detection of cytokines IL-1ß, IL-6, TNFα, IL-10, IFNγ, IL-4 and IL-17 in the CG as well as its potential usefulness in its early detection. These biomarkers were selected for the advantage they would have of being non-invasive methods that could improve the detection, treatment and prognosis of this disease.


Subject(s)
Humans , Male , Female , Stomach Neoplasms/drug therapy , Biomarkers , Receptors, Urokinase Plasminogen Activator , Stomach Neoplasms/mortality , Mortality , Helicobacter pylori , Interleukin-4 , Interleukin-6 , Interleukin-1 , Interleukin-10 , Interleukin-17
6.
Article in English | WPRIM | ID: wpr-762178

ABSTRACT

PURPOSE: Immunological mechanisms underlying asthma exacerbation have not been elucidated. The aim of this study was to assess the associations of various asthma exacerbation traits with selected serum microRNA (miRNA) expression and T-cell subpopulations. METHODS: Twenty-one asthmatics were studied during asthma exacerbation (exacerbation visit [EV] and the follow-up visit [FV] at 6 weeks). At both visits, spirometry was performed, fractional exhaled nitric oxide (FeNO) was measured, and nasopharyngeal and blood samples were collected. In nasopharyngeal samples, respiratory viruses were assayed by multiplex polymerase chain reaction (PCR), and bacterial cultures were performed. Serum miRNAs were assayed with real-time PCR. T-cell surface markers, eosinophil progenitors and intracellular cytokines were assessed by flow cytometry. RESULTS: Two-thirds of patients had moderate or severe exacerbation and the FV, overall improvement in asthma control was observed. The mean expression of serum miRNA-126a, miRNA-16 and miRNA-21 was significantly lower at the EV than at the FV. At EV, miRNA-29b correlated with FeNO (r = 0.44, P < 0.05), and 5 of 7 miRNA tested correlated with pulmonary function tests. The number of cluster of differentiation (CD)45+CD4+interleukin (IL)4+ cells was significantly higher at the EV than at the FV, and positive correlations of T-regulatory cells and eosinophil progenitors with asthma control was found. At the EV, serum miRNAs negatively correlated with the number of T cells expressing IL-4, IL-17, IL-22 and interferon gamma, while at the FV both positive and negative correlations with T-cell subsets were observed. No association of detected pathogen (viruses and bacteria) in nasopharyngeal fluid with clinical, functional and immunological parameters was found. CONCLUSIONS: Epigenetic dysregulation during asthma exacerbation could be related to respiratory function, airway inflammation and T-cell cytokine expression.


Subject(s)
Asthma , Cytokines , Disease Progression , Eosinophils , Epigenomics , Flow Cytometry , Follow-Up Studies , Humans , Inflammation , Interferons , Interleukin-17 , Interleukin-4 , MicroRNAs , Multiplex Polymerase Chain Reaction , Nitric Oxide , Real-Time Polymerase Chain Reaction , Respiratory Function Tests , Spirometry , T-Lymphocyte Subsets , T-Lymphocytes
7.
Braz. j. otorhinolaryngol. (Impr.) ; 85(3): 337-343, May-June 2019. tab, graf
Article in English | LILACS | ID: biblio-1011621

ABSTRACT

Abstract Introduction: Burnt sugarcane harvesting requires intense physical exertion in an environment of high temperature and exposure to particulate matter. Objective: To evaluate the effects of burnt sugarcane harvesting on rhinitis symptoms and inflammatory markers in sugarcane workers. Methods: A total of 32 male sugarcane workers were evaluated with questionnaire for rhinitis symptoms, and for inflammatory markers on peripheral blood and nasal lavage, in the non-harvesting, and 3 and 6 months into the sugarcane harvesting period. Weather data and particulate matter fine concentrations were measured in the same day. Results: The particulate matter concentrations in sugarcane harvesting were 27 (23-33 µg/m3), 112 (96-122 µg/m3), and 63 (17-263 µg/m3); 24 h temperatures were 32.6 (25.4-37.4 ºC), 32.3 (26.7-36.7 ºC) and 29.7 (24.1-34.0 ºC) and relative humidities were 45.4 (35.0-59.7%), 47.9 (39.1-63.0%), and 59.9 (34.7-63.2%) in the non-harvesting period, three and 6 months of the harvesting period. The age was 37.4 ± 10.9 years. The prevalence of rhinitis symptoms was significantly higher at 3 months of the harvesting period (53.4%), compared to non-harvesting period (26.7%; p = 0.039) and at 6 months into the harvesting period (20%; p = 0.006). Concentrations of interleukin 6 (IL-6) in nasal lavage increased after 3 months of the harvesting period compared to the non-harvesting period (p = 0.012). The presence of rhinitis symptoms, after 3 months of the harvesting period, was directly associated with blood eosinophils and inversely associated with neutrophils. Conclusions: After 3 months of work in burnt sugarcane harvesting the prevalence of rhinitis symptoms and IL-6 in nasal lavage increased. Furthermore, eosinophil counts were directly associated with the rhinitis symptoms in the period of higher concentration of particulate matter.


Resumo Introdução: A colheita de cana-de-açúcar queimada requer esforço físico intenso em um ambiente com altas temperaturas e exposição a material particulado. Objetivo: Avaliar os efeitos da colheita de cana-de-açúcar queimada nos sintomas de rinite e marcadores inflamatórios de cortadores de cana-de-açúcar. Método: Foram avaliados 32 cortadores de cana-de-açúcar do sexo masculino por meio de um questionário para sintomas de rinite, e marcadores inflamatórios em sangue periférico e lavado nasal, no período de entressafra, e em 3 e 6 meses após o início da colheita da cana-de-açúcar. Os dados climáticos e as concentrações de material particulado fino foram medidos no mesmo dia. Resultados: O material particulado fino na entressafra e em 3 e 6 meses de safra foi 27 (23-33 µg/m3), 112 (96-122 µg/m3) e 63 (17-263 µg/m3), respectivamente; a temperatura de 24 horas foi 32,6 (25,4º-37,4ºC), 32,3 (26,7º-36,7ºC) e 29,7 (24,1º-340ºC) e a umidade relativa do ar foi 45,4 (35,0%-59,7%), 47,9 (39,1%-63,0%), e 59,9 (34,7%-63,2%), na entressafra, 3 e 6 meses após o início da colheita. A idade foi de 37,4 ± 10,9 anos. A prevalência de sintomas de rinite foi significativamente maior em 3 meses da S (53,4%), comparado com a entressafra (26,7%; p = 0,039) e 6 meses da safra (20%; p = 0,006). As concentrações de interleucina 6 (IL-6) no lavado nasal aumentaram após 3 meses do início da colheita comparado com a entressafra (p = 0,012). A presença de sintomas de rinite, após 3 meses do início da colheita, foi diretamente associada com eosinófilos e inversamente associada com neutrófilos. Conclusões: Após 3 meses do início da colheita da cana-de-açúcar queimada, houve aumento na prevalência de sintomas de rinite e IL-6 em LN. Além disso, as contagens de eosinófilos foram diretamente associadas aos sintomas de rinite no período de maior concentração de material particulado.


Subject(s)
Humans , Male , Adult , Rhinitis/etiology , Saccharum , Air Pollutants, Occupational/adverse effects , Particulate Matter/adverse effects , Occupational Diseases/etiology , Biomarkers/blood , Rhinitis/blood , Prevalence , Interleukin-4/blood , Interleukin-6/blood , Agriculture , Occupational Diseases/blood
8.
Einstein (Säo Paulo) ; 17(4): eRC4599, 2019. graf
Article in English | LILACS | ID: biblio-1012009

ABSTRACT

ABSTRACT Case report of a patient with severe atopic dermatitis who showed a good response to dupilumab. She had already used two immunosuppressive agents, cyclosporine A and mycophenolate mofetil, for the treatment of atopic dermatitis with no proper control of the disease. She had also been taking all measures to control severe cases of the disease: bath and environmental controls, topical potent corticosteroids and emollients. She presented constant pruritus and skin lesions, frequent skin infections e poor quality of life. She also developed depression due to her disease. Recently, dupilumab, a new biological agent, was approved for the treatment of moderate/severe atopic dermatitis in many countries, including Brazil. Dupilumab is a monoclonal antibody with a common alpha chain of interleukin (IL) 4 and IL-13 receptors, two cytokines involved in the Th2 profile immune response that promote atopic inflammation. In a pioneer way in Brazil, the patient initiated the treatment with an attack dose of 600mg subcutaneous of dupilumab and 300mg subcutaneous every other week. Up to now, she has taken four applications, presenting a great improvement of the disease and her quality of life. There were no adverse effects, nor in the injection site nor of other kind. Patient and her family are very satisfied, and the medical team evaluates that the treatment is being well succeed. The case report described here subsidizes the use of dupilumab in the treatment of severe atopic dermatitis refractory to use of immunosuppressive agents.


RESUMO Relatamos o caso de uma paciente com dermatite atópica grave, que mostrou boa resposta ao dupilumabe. Ela já tinha usado dois agentes imunossupressores, a ciclosporina A e o micofenolato de mofetila, para o tratamento da dermatite atópica, sem obter o controle adequado da doença. Ela também vinha fazendo uso de todas as medidas de controle para casos graves da doença: cuidados com o banho, controle ambiental, corticosteroides potentes tópicos e emolientes. Apresentava prurido e lesões cutâneas constantes, infeções de pele frequentes e qualidade de vida ruim. Passou a apresentar depressão devido à sua doença. Recentemente, o dupilumabe, um agente biológico novo, foi aprovado para o tratamento de dermatite atópica moderada a severa em muitos países, incluindo o Brasil. Dupilumabe é um anticorpo monoclonal cujo alvo é a cadeia alfa comum aos receptores da interleucina (IL) 4 e IL-13, duas citocinas envolvidas no perfil de resposta imune Th2, que promove inflamação atópica. De modo pioneiro no Brasil, a paciente iniciou o tratamento, com dose de ataque de 600mg por via subcutânea de dupilumabe e 300mg também por via subcutânea a cada 2 semanas. Até o momento deste relato, ela realizou quatro aplicações, apresentando grande melhora da doença e da qualidade de vida. Não houve efeitos adversos, nem no local da injeção e nem de outro tipo. A paciente e sua família estão muito satisfeitas, e os médicos que a tratam avaliam que a terapia está sendo bem-sucedida. Este relato de caso subsidia o uso de dupilumabe no tratamento da dermatite atópica grave refratária ao uso de imunossupressores.


Subject(s)
Humans , Female , Adolescent , Dermatitis, Atopic/drug therapy , Immunosuppressive Agents/administration & dosage , Antibodies, Monoclonal/administration & dosage , Quality of Life , Severity of Illness Index , Brazil , Immunosuppression , Interleukin-4 , Interleukin-13 , Antibodies, Monoclonal, Humanized , Injections, Subcutaneous
9.
Article in English | WPRIM | ID: wpr-761718

ABSTRACT

The roles of mast cells in allergic diseases and helminth infections are well known. However, the roles of mast cells in T. gondii infection is poorly understood. This study was focused on the production of pro-inflammatory cytokines (TNF-α, IL-4), chemokines (CXCL8, MCP-1) and nitric oxide (NO) by mast cells in response to soluble lysate of T. gondii tachyzoites. Production of CXCL8 (IL-8), MCP-1, TNF-α and IL-4 were measured by RT-PCR and ELISA. Western blot were used for detection of CXCR-1 and CXCR2. Our results showed that T. gondii lysates triggered mast cells to release CXCL8, MCP-1, TNF-α, IL-4 and to produce NO. This suggests that mast cells play an important role in inflammatory responses to T. gondii.


Subject(s)
Blotting, Western , Chemokines , Cytokines , Enzyme-Linked Immunosorbent Assay , Helminths , Humans , Interleukin-4 , Mast Cells , Nitric Oxide , Toxoplasma
10.
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 , 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 , Mice , Nasal Mucosa , Ovalbumin , Ovum , Rhinitis, Allergic , RNA, Messenger , Spleen , Th2 Cells , Tumor Necrosis Factor-alpha
11.
Article in English | WPRIM | ID: wpr-763022

ABSTRACT

Udenafil, which is a PDE5 inhibitor, is used to treat erectile dysfunction. However, it is unclear whether udenafil induces hair growth via the stimulation of adipose-derived stem cells (ASCs). In this study, we investigated whether udenafil stimulates ASCs and whether increased growth factor secretion from ASCs to facilitate hair growth. We found that subcutaneous injection of udenafil-treated ASCs accelerated telogen-to-anagen transition in vivo. We also observed that udenafil induced proliferation, migration and tube formation of ASCs. It also increased the secretion of growth factors from ASCs, such as interleukin-4 (IL-4) and IL12B, and the phosphorylation of ERK1/2 and NFκB. Furthermore, concomitant upregulation of IL-4 and IL12B mRNA levels was attenuated by ERK inhibitor or NFκB knockdown. Application of IL-4 or IL12B enhanced anagen induction in mice and increased hair follicle length in organ culture. The results indicated that udenafil stimulates ASC motility and increases paracrine growth factor, including cytokine signaling. Udenafil-stimulated secretion of cytokine from ASCs may promote hair growth via the ERK and NFκB pathways. Therefore, udenafil can be used as an ASC-preconditioning agent for hair growth.


Subject(s)
Animals , Erectile Dysfunction , Hair Follicle , Hair , Injections, Subcutaneous , Intercellular Signaling Peptides and Proteins , Interleukin-4 , Male , Mice , Organ Culture Techniques , Phosphorylation , RNA, Messenger , Stem Cells , Up-Regulation
12.
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)
Allergy and Immunology , Animals , Anti-Allergic Agents , Asthma , Biopsy , Dermatitis , Dermatitis, Atopic , Enzyme-Linked Immunosorbent Assay , Glucosamine , Immunoglobulin E , Immunoglobulins , Interleukin-13 , Interleukin-17 , Interleukin-4 , Interleukins , Mice , Models, Animal , Rhinitis , Skin , Therapeutic Uses
13.
Article in English | WPRIM | ID: wpr-762158

ABSTRACT

PURPOSE: This study aimed to investigate the impact of short-term haze exposure on nasal inflammation in healthy volunteers. METHODS: Thirty-three healthy university students were assessed for nasal symptoms, nasal patency, upper and lower respiratory tract nitric oxide (NO) as well as inflammatory mediators and neuropeptides in nasal secretions before and after a 5-day haze episode. Peripheral blood mononuclear cells (PBMCs) were stimulated with particulate matter with an aerodynamic diameter of less than 2.5 μm (PM(2.5)), and cytokines in the supernatants were examined. RESULTS: Mild nasal symptoms were reported by some participants during the haze episode. Objective measures of nasal patency demonstrated that nasal airway resistance was significantly increased from baseline levels, while nasal cavity volume and minimum cross-sectional area were significantly decreased. Similarly, the levels of nasal and exhaled NO, eotaxin, interleukin (IL)-5, chemokine (C-C motif) ligand 17, IL-8, substance P, nerve growth factor and vasoactive intestinal peptides in nasal secretions were significantly increased from baseline values following the haze episode. In contrast, the levels of interferon-γ, IL-10, transforming growth factor-β and neuropeptide Y were significantly decreased. Incubation with 0.1-10 μg/mL PM(2.5) significantly increased release of IL-1β, IL-4, IL-5, IL-8 and IL-10 from PBMCs. CONCLUSIONS: Short-term haze exposure may lead to nasal inflammation and hypersensitivity in healthy subjects predominantly by Th2 cytokine-mediated immune responses.


Subject(s)
Air Pollution , Airway Resistance , Cytokines , Healthy Volunteers , Humans , Hypersensitivity , Inflammation , Interleukin-10 , Interleukin-4 , Interleukin-5 , Interleukin-8 , Interleukins , Nasal Cavity , Nerve Growth Factor , Neuropeptide Y , Neuropeptides , Nitric Oxide , Particulate Matter , Peptides , Respiratory System , Substance P
14.
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)
Bias , Biomarkers , Cytokines , Humans , 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
15.
Psychiatry Investigation ; : 177-184, 2019.
Article in English | WPRIM | ID: wpr-760920

ABSTRACT

OBJECTIVE: Schizophrenia is a disabling disorder of unknown aetiology, lacking definite diagnostic method and cure. A reliable biological marker of schizophrenia is highly demanded, for which traceable immune mediators in blood could be promising candidates. We aimed to gather the best findings of neuroinflammatory markers for first-episode psychosis (FEP). METHODS: We performed an extensive narrative review of online literature on inflammation-related markers found in human FEP patients only. RESULTS: Changes to cytokine levels have been increasingly reported in schizophrenia. The peripheral levels of IL-1 (or its receptor antagonist), soluble IL-2 receptor, IL-4, IL-6, IL-8, and TNF-α have been frequently reported as increased in FEP, in a suggestive continuum from high-risk stages for psychosis. Microglia and astrocytes establish the link between this immune signalling and the synthesis of noxious tryptophan catabolism products, that cause structural damage and directly hamper normal neurotransmission. Amongst these, only 3-hydroxykynurenine has been consistently described in the blood of FEP patients. CONCLUSION: Peripheral molecules stemming from brain inflammation might provide insightful biomarkers of schizophrenia, as early as FEP or even prodromal phases, although more time- and clinically-adjusted studies are essential for their validation.


Subject(s)
Astrocytes , Biomarkers , Encephalitis , Humans , Interleukin-1 , Interleukin-4 , Interleukin-6 , Interleukin-8 , Metabolism , Methods , Microglia , Polytetrafluoroethylene , Psychotic Disorders , Receptors, Interleukin-2 , Schizophrenia , Synaptic Transmission , Tryptophan
16.
Natural Product Sciences ; : 261-267, 2019.
Article in English | WPRIM | ID: wpr-760562

ABSTRACT

The rhizomes of Dioscorea japonica Thunb. are widely consumed as food and also used to treat diabetes and polyuria in Korea. This study was undertaken to study the anti-atopic dermatitis effects of a 95% ethanolic extract (DJE) of D. japonica in an oxazolone-stimulated murine model of atopic dermatitis (AD). The therapeutic effects of DJE on AD-like skin lesions were assessed on both ears. DJE (1%) or dexamethasone (0.5%; the positive control) were applied to skin lesions for three weeks. Serum levels of IgE and IL-4 were assessed by ELISA (enzyme-linked immunosorbent assay). Histopathological examinations were performed by hematoxylin and eosin (H&E) and toluidine blue staining and revealed DJE significantly reduced dermal thickness and inflammatory cell infiltration when applied to oxazolone-treated ear skin. DJE-treated AD mice also showed lower serum levels of IgE and IL-4 than oxazolone-stimulated controls. Our findings demonstrate DJE might be a useful safe, topical agent for the treatment of atopic diseases.


Subject(s)
Animals , Dermatitis , Dermatitis, Atopic , Dexamethasone , Dioscorea , Ear , Enzyme-Linked Immunosorbent Assay , Eosine Yellowish-(YS) , Ethanol , Hematoxylin , Immunoglobulin E , Interleukin-4 , Korea , Mice , Oxazolone , Polyuria , Rhizome , Skin , Therapeutic Uses , Tolonium Chloride
17.
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)
Administration, Intranasal , Animals , 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 , Mice , Models, Animal , Ovalbumin , Ovum , Rhinitis, Allergic , RNA, Messenger , Vitamin D
18.
Article in English | WPRIM | ID: wpr-719450

ABSTRACT

BACKGROUND/AIMS: This study aimed to determine the regulatory role of N-acetyl-l-cysteine (NAC), an antioxidant, in interleukin 17 (IL-17)-induced osteoclast differentiation in rheumatoid arthritis (RA). METHODS: After RA synovial fibroblasts were stimulated by IL-17, the expression and production of receptor activator of nuclear factor κ-B ligand (RANKL) was determined by real-time polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). Osteoclastogenesis was also determined after co-cultures of IL-17-stimulated RA synovial fibroblasts, Th17 cells and various concentrations of NAC with monocytes. After human peripheral CD4⁺ T cells were cultured with NAC under Th17 condition, IL-17, interferon γ, IL-4, Foxp3, RANKL, and IL-2 expression and production was determined by flow cytometry or ELISA. RESULTS: When RA synovial fibroblasts were stimulated by IL-17, IL-17 stimulated the production of RANKL, and NAC reduced the IL-17-induced RANKL production in a dose-dependent manner. NAC decreased IL-17-activated phosphorylation of mammalian target of rapamycin, c-Jun N-terminal kinase, and inhibitor of κB. When human peripheral blood CD14⁺ monocytes were cultured with macrophage colony-stimulating factor and IL-17 or RANKL, osteoclasts were differentiated, and NAC reduced the osteoclastogenesis. After human peripheral CD4⁺ T cells were co-cultured with IL-17-pretreated RA synovial fibroblasts or Th17 cells, NAC reduced their osteoclastogenesis. Under Th17 polarizing condition, NAC decreased Th17 cell differentiation and IL-17 and RANKL production. CONCLUSIONS: NAC inhibits the IL-17-induced RANKL production in RA synovial fibroblasts and IL-17-induced osteoclast differentiation. NAC also reduced Th17 polarization. NAC could be a supplementary therapeutic option for inflammatory and bony destructive processes in RA.


Subject(s)
Acetylcysteine , Arthritis, Rheumatoid , Coculture Techniques , Enzyme-Linked Immunosorbent Assay , Fibroblasts , Flow Cytometry , Humans , Interferons , Interleukin-17 , Interleukin-2 , Interleukin-4 , JNK Mitogen-Activated Protein Kinases , Macrophage Colony-Stimulating Factor , Monocytes , Osteoclasts , Osteogenesis , Phosphorylation , RANK Ligand , Real-Time Polymerase Chain Reaction , Sirolimus , T-Lymphocytes , Th17 Cells
19.
Journal of Experimental Hematology ; (6): 1321-1324, 2019.
Article in Chinese | WPRIM | ID: wpr-775721

ABSTRACT

Abstract  Immune thrombocytopenia (ITP) is an acquired autoimmune hemorrhagic disease, although the ITP pathogenesis is completely unknown, but in terms of the current view, the immune tolerance is main reason for the onset of ITP. In recent years, more and more immune cell subsets, cytokines and the new approacher were found to be closely related with the ITP, such as saliva acid, B cell activating factor, dysfunction of regulatory B cells and Th1/Th2 balance drift, CD4 CD25 T cell function defect, IL-23/Th17 pathway regulation, etc., In this paper, the latest research progress on the immune pathogenesis of ITP are reviewed, so as to provide theoretical basis and research direction for further understanding the pathogenesis of ITP.


Subject(s)
Cytokines , Humans , Interleukin-4 , Purpura, Thrombocytopenic, Idiopathic , Th17 Cells
20.
Acta cir. bras ; 33(6): 491-498, June 2018. graf
Article in English | LILACS | ID: biblio-949359

ABSTRACT

Abstract Purpose: To investigate the possible role of IL-4 signaling pathway in vincristine-induced peripheral neuropathy. Methods: The mouse model of vincristine-induced peripheral neuropathy and interleukin (IL)-4 knockout mice were utilized to investigate the possible role of IL-4 signaling pathway in vincristine-induced peripheral neuropathy. Vincristine induced increased sensitivity to mechanical stimulation was measured by von Frey hair test 7 and 14 days after intraperitoneal administration of 0.1 mg/kg vincristine in mice. Relative expression levels of cytokines were detected by quantitative real-time PCR. STAT6 expression following vincristine treatment was assessed with western blotting. Results: We discovered that IL-4/STAT6 signaling was down-regulated in vincristine-treated mice. Deletion of IL-4 in mice increased the sensitivity to mechanical allodynia. IL-4 knockout mice also produced more pro-inflammatory cytokines, including IL-1β and TNF-α. Notably, co-administration of exogenous recombination IL-4 significantly prevented vincristine-induced mechanical allodynia. Conclusion: Anti-inflammatory cytokine IL-4 protects rodent model from vincristine-induced peripheral neuropathy via the stimulation of IL-4/STAT6 signaling and inhibition of the pro-inflammatory cytokines.


Subject(s)
Animals , Male , Vincristine/adverse effects , Interleukin-4/pharmacology , Peripheral Nervous System Diseases/prevention & control , STAT6 Transcription Factor/drug effects , Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents, Phytogenic/adverse effects , Time Factors , Down-Regulation/drug effects , Blotting, Western , Reproducibility of Results , Cytokines/analysis , Cytokines/drug effects , Treatment Outcome , Mice, Knockout , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/metabolism , Neuroprotective Agents , Disease Models, Animal , STAT6 Transcription Factor/analysis , Real-Time Polymerase Chain Reaction , Hyperalgesia/chemically induced , Hyperalgesia/drug therapy , Mice, Inbred C57BL
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