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1.
Braz. j. infect. dis ; 23(1): 27-33, Jan.-Feb. 2019. tab, graf
Article in English | LILACS | ID: biblio-1001503

ABSTRACT

ABSTRACT Introduction: Human T-cell lymphotropic virus type 1 (HTLV-1) is sexually transmitted and causes persistent infection. This virus induces activation of the immune system and production of inflammatory cytokines. This study aimed to assess the cytokine profile and cytopathological findings in the cervicovaginal fluid of asymptomatic HTLV-1-infected women. Methods: HTLV-1-infected and uninfected women were selected at the Centro de Atendimento ao Portador de HTLV in Salvador-Brazil. None of the included HTLV-1-infected women reported any HTLV-1-associated diseases. All volunteers underwent gynecological examination to collect cervicovaginal fluid. Cytokine quantification was performed using the Cytometric Bead Array (CBA) Human Th1/Th2/Th17 kit. Light microscopy was used to evaluate cervicovaginal cytopathology. In addition, proviral load in cervicovaginal fluid and peripheral blood was measured by real-time quantitative polymerase chain reaction. Results: 112 women (63 HTLV-1-infected and 49 uninfected) were evaluated. No differences were found with respect to cytopathological cervicovaginal findings between the groups. IL-2, TNF, IL-4, IL-10, and IL-17 levels were significantly higher in cervicovaginal fluid of the HTLV-1-infected women than in uninfected women (p < 0.05). Conversely, IFN-γ was found to be lower in the HTLV-1-infected women (p < 0.001) compared to uninfected individuals. Cervicovaginal proviral load was detectable in 53% of the HTLV-1-infected women and was found to be consistently lower than the proviral load in peripheral blood. Conclusions: HTLV-1 infection induces immune activation in cervicovaginal environment, characterized by elevated concentrations of Th1, Th2, and IL17 in the cervicovaginal fluid.


Subject(s)
Humans , Female , Adult , Vagina/pathology , Body Fluids/chemistry , HTLV-I Infections/pathology , Cervix Uteri/pathology , Cytokines/analysis , Social Class , Vagina/immunology , Vagina/virology , Body Fluids/immunology , Enzyme-Linked Immunosorbent Assay , Leukocytes, Mononuclear/virology , Human T-lymphotropic virus 1/isolation & purification , HTLV-I Infections/immunology , HTLV-I Infections/virology , Cervix Uteri/immunology , Cervix Uteri/virology , Cross-Sectional Studies , Th2 Cells/immunology , Th1 Cells/immunology , Statistics, Nonparametric , Viral Load , Interleukin-17/immunology
2.
Rev. Soc. Bras. Med. Trop ; 52: e20180172, 2019. tab, graf
Article in English | LILACS | ID: biblio-1041541

ABSTRACT

Abstract INTRODUCTION: American tegumentary leishmaniasis (ATL) and leprosy share common areas of prevalence, but reports of coinfection are scarce. METHODS: We report a series of 9 ATL-leprosy cases and discuss the association. An integrative diagram to analyze the clinico-immunological features of coinfection with both diseases. RESULTS: Nine patients with leishmaniasis (5 cutaneous, 3 mucocutaneous, 1 disseminated case) exhibited concurrent infection with distinct clinical forms of leprosy. Our diagram-based analysis evidenced a divergent clinico-immunological spectrum for each disease in 8 out of 9 cases. CONCLUSIONS: The spectrum of ATL-leprosy comorbidity suggests that the host has a specific immune response against each pathogen.


Subject(s)
Humans , Male , Female , Aged , Aged, 80 and over , Leishmaniasis, Cutaneous/immunology , Th2 Cells/immunology , Th1 Cells/immunology , Leprosy/immunology , Leishmaniasis, Cutaneous/complications , Coinfection/immunology , Leprosy/complications , Middle Aged
3.
Arq. neuropsiquiatr ; 76(5): 339-345, May 2018. tab, graf
Article in English | LILACS | ID: biblio-950537

ABSTRACT

ABSTRACT Neurocysticercosis (NCC) is one of the parasitic infections that most affects the central nervous system. The knowledge regarding its immunopathogenesis and pathophysiology needs broadening. Taenia crassiceps cysticerci are used as the NCC experimental model. The aim of this work was to describe the general pathological processes and the in situ cytokine profile in C57BL/6 mice inoculated intracranially with viable T. crassiceps cysticerci. The histopathology analysis showed cysticerci in the extraparenchymal and intraventricular region, mononuclear inflammatory infiltration surrounding the parasite, microgliosis and meningitis. The analysis of the in situ immune profiles showed a predominance of the Th2 response. The IL-4 and IL-10 dosages were significantly increased in the infected group. The decrease in the INF-gamma dosage reflects the immunomodulation from the cysticerci. In conclusion, a T. crassiceps NCC infection in C57BL/6 mice triggers an inflammatory response, a predominance of Th2 type in situ profile, with mononuclear inflammatory cell infiltration, meningitis and microgliosis.


RESUMO Neurocisticercose (NCC) é uma das doenças parasitárias que mais afeta o sistema nervoso central. É necessário aprofundar o conhecimento em relação à sua imunopatogênese e patofisiologia. Os cisticercos de Taenia crassiceps são utilizados como modelo experimental para estudos da NCC. O objetivo deste trabalho foi descrever os processos patológicos gerais e o perfil de citocinas in situ em camundongos C57BL/6 inoculados via intracerebral com cisticercos viáveis de T. crassiceps. A análise histopatológica demonstrou cisticercos nas regiões extra-parenquimatosa e intraventricular, infiltrado inflamatório de células mononucleares ao redor do parasita, microgliose e meningite. A análise in situ do perfil de citocinas mostrou uma predominância da resposta Th2. As dosagens de IL-4 e IL-10 foram significativamente maiores no grupo infectado. Conclui-se que a NCC por T. crassiceps em camundongos C57BL/6 induz uma resposta inflamatória com predominância in situ de citocinas do perfil Th2, com infiltrado inflamatório de células mononucleares, meningite e microgliose.


Subject(s)
Animals , Female , Rats , Interleukin-4/blood , Interferon-gamma/blood , Interleukin-10/blood , Th2 Cells/immunology , Neurocysticercosis/immunology , Taenia/immunology , Enzyme-Linked Immunosorbent Assay , Interleukin-4/immunology , Interferon-gamma/immunology , Interleukin-10/immunology , Neurocysticercosis/pathology , Disease Models, Animal , Mice, Inbred C57BL
4.
Braz. j. infect. dis ; 22(2): 142-145, Mar.-Apr. 2018. tab
Article in English | LILACS | ID: biblio-1039213

ABSTRACT

ABSTRACT The HIV-1 initial viral infection may present diverse clinical and laboratory course and lead to rapid, intermediate, or long-term progression. Among the group of non-progressors, the elite controllers are those who control the infection most effectively, in the absence of antiretroviral therapy (ART). In this paper, the TH1, TH2 and TH17 cytokines profiles are described, as well as clinical and laboratory aspects of an HIV-infected patient with undetectable viral load without antiretroviral therapy. Production of IL-6, IL-10, TNF-α, IFN-γ, and IL-17 was detected; in contrast IL-4 was identified. Host-related factors could help explain such a level of infection control, namely the differentiated modulation of the cellular immune response and a non-polarized cytokine response of the TH1 and TH2 profiles.


Subject(s)
Humans , Female , Adult , HIV Infections/immunology , Cytokines/immunology , HIV-1 , HIV Long-Term Survivors , CD4-Positive T-Lymphocytes/immunology , HIV Infections/blood , HIV Infections/virology , Th2 Cells/immunology , Th1 Cells/immunology , CD8-Positive T-Lymphocytes/immunology , Viral Load , Antiretroviral Therapy, Highly Active , Immunity, Cellular/immunology
5.
Rev. bras. reumatol ; 57(5): 461-465, Sept.-Oct. 2017.
Article in English | LILACS | ID: biblio-899455

ABSTRACT

Abstract Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease, with a progressive course, characterized by chronic synovitis that may evolve with deformities and functional disability, and whose early treatment minimizes joint damage. Its etiopathogenesis is not fully elucidated but comprises immunologic responses mediated by T helper cells (Th1). An apparent minor severity of RA in patients from regions with lower income could be associated with a higher prevalence of gut parasites, especially helminths. Strictly, a shift in the immune response toward the predominance of T helper cells (Th2), due to the chronic exposure to helminths, could modulate negatively the inflammation in RA patients, resulting in lower severity/joint injury. The interaction between the immunological responses of parasitic helminths in rheumatoid arthritis patients is the purpose of this paper.


Resumo A artrite reumatoide (AR) é uma doença inflamatória autoimune, sistêmica, de curso progressivo, caracterizada por exuberante sinovite crônica, que pode gerar deformidades e incapacidade funcional, cujo tratamento precoce minimiza o dano às juntas. Sua etiopatogenia ainda não está completamente elucidada, mas compreende respostas imunológicas com a participação de células T auxiliares (Th1). Uma aparente menor gravidade da AR em pacientes de regiões com menor renda poderia estar associada a maior prevalência de parasitoses intestinais, especialmente as helmintíases. A rigor, um desvio na resposta imune para o predomínio de células T auxiliares (Th2), decorrente da exposição crônica a helmintos, modularia negativamente a inflamação em doentes com AR, e levaria a menor gravidade e dano articular. A revisão de aspectos da influência da reposta imunológica nas parasitoses intestinais, especialmente as helmintíases, em pacientes com artrite reumatoide é o objetivo desse trabalho.


Subject(s)
Humans , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/parasitology , Helminthiasis/immunology , Severity of Illness Index , Th2 Cells/immunology , Th2 Cells/parasitology , Th1 Cells/immunology , Th1 Cells/parasitology , Immunomodulation , Protective Factors , Helminthiasis/complications
6.
Rev. Soc. Bras. Med. Trop ; 50(2): 208-215, Mar.-Apr. 2017. tab, graf
Article in English | LILACS | ID: biblio-842843

ABSTRACT

Abstract INTRODUCTION: Currently, there are no laboratory tests or sensitive and specific molecular markers for the early diagnosis of leprosy. The aim of this study was to analyze the clinical characteristics of patients with leprosy and investigate their immunological profile, comparing this with the type of lesion and the presence or absence of a Bacillus Calmette-Guérin (BCG) vaccination scar. METHODS: Statistical analyzes were performed by employing comparative tests (Pearson´s chi-square) to evaluate the variables in different clinical forms, considering significance at the 5% level. RESULTS: The study identified a predominance of lepromatous leprosy (26.9%) in patients aged between 34-53 years. Caucasians predominantly had borderline tuberculoid (BT) clinical forms (42%); a predominance of males with borderline lepromatous (19%) and lepromatous leprosy (26.9%) forms was observed; and the presence of BCG vaccination scars (27.5%) and lower limb nerves were more affected (38%) predominantly in the BT clinical form. Significant differences were identified, which included hypochromic lesions predominantly in the BT clinical form (24%); diffuse-type lesions predominantly in the tuberculoid (TT) clinical form (28%); ill-defined lesion border dominance in lepromatous leprosy (LL) clinical forms (30%); an irregular lesion limit predominantly in LL clinical forms (32%); and a predominant Th1 immune response in the BT clinical form (41.7%). CONCLUSIONS: The evaluation of the immunological profile in leprosy patients may contribute to the more detailed diagnosis and possibly better characterization of the prognosis for these individuals.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Young Adult , Th2 Cells/immunology , Th1 Cells/immunology , Leprosy, Multibacillary/diagnosis , Leprosy, Multibacillary/immunology , Leprosy, Paucibacillary/diagnosis , Leprosy, Paucibacillary/immunology , Biopsy , Cross-Sectional Studies , Fluorescent Antibody Technique , Th1 Cells/metabolism , Leprosy, Multibacillary/classification , Leprosy, Paucibacillary/classification , Middle Aged
7.
Braz. j. med. biol. res ; 50(8): e5991, 2017. graf
Article in English | LILACS | ID: biblio-888980

ABSTRACT

Asthma is a chronic allergic disease characterized by airway inflammation, airway hyper-responsiveness (AHR), and mucus hypersecretion. T-lymphocytes are involved in the pathogenesis of asthma, mediating airway inflammatory reactions by secreting cytokines. The phosphoinositide 3-kinase (PI3K) and Notch signaling pathways are associated with T cell signaling, proliferation, and differentiation, and are important in the progression of asthma. Thus, compounds that can modulate T cell proliferation and function may be of clinical value. Here, we assessed the effects of tangeretin, a plant-derived flavonoid, in experimental asthma. BALB/c mice at postnatal day (P) 12 were challenged with ovalbumin (OVA). Separate groups of mice (n=18/group) were administered tangeretin at 25 or 50 mg/kg body weight by oral gavage. Dexamethasone was used as a positive control. Tangeretin treatment reduced inflammatory cell infiltration in bronchoalveolar lavage fluid (BALF) and also restored the normal histology of lung tissues. OVA-specific IgE levels in serum and BALF were reduced. AHR, as determined by airway resistance and lung compliance, was normalized. Flow cytometry analyses revealed a reduced Th17 cell population. Tangeretin reduced the levels of Th2 and Th17 cytokines and raised IFN-γ levels. PI3K signaling was inhibited. The expressions of the Notch 1 receptor and its ligands Jagged 1 and 2 were downregulated by tangeretin. Our findings support the possible use of tangeretin for treating allergic asthma.


Subject(s)
Animals , Mice , Asthma/drug therapy , Signal Transduction/drug effects , Anti-Asthmatic Agents/therapeutic use , Flavones/therapeutic use , Asthma/immunology , Cytokines/drug effects , Cytokines/immunology , Th2 Cells/drug effects , Th2 Cells/immunology , Th1 Cells/drug effects , Th1 Cells/immunology , Disease Models, Animal , Proto-Oncogene Proteins c-akt/drug effects , Proto-Oncogene Proteins c-akt/immunology , Th17 Cells/drug effects , Th17 Cells/immunology , Animals, Newborn , Mice, Inbred BALB C
8.
Braz. j. med. biol. res ; 49(5): e5209, 2016. tab, graf
Article in English | LILACS | ID: biblio-951671

ABSTRACT

The traditional concept that effector T helper (Th) responses are mediated by Th1/Th2 cell subtypes has been broadened by the recent demonstration of two new effector T helper cells, the IL-17 producing cells (Th17) and the follicular helper T cells (Tfh). These new subsets have many features in common, such as the ability to produce IL-21 and to express the IL-23 receptor (IL23R), the inducible co-stimulatory molecule ICOS, and the transcription factor c-Maf, all of them essential for expansion and establishment of the final pool of both subsets. Tfh cells differ from Th17 by their ability to home to B cell areas in secondary lymphoid tissue through interactions mediated by the chemokine receptor CXCR5 and its ligand CXCL13. These CXCR5+ CD4+ T cells are considered an effector T cell type specialized in B cell help, with a transcriptional profile distinct from Th1 and Th2 cells. The role of Tfh cells and its primary product, IL-21, on B-cell activation and differentiation is essential for humoral immunity against infectious agents. However, when deregulated, Tfh cells could represent an important mechanism contributing to exacerbated humoral response and autoantibody production in autoimmune diseases. This review highlights the importance of Tfh cells by focusing on their biology and differentiation processes in the context of normal immune response to infectious microorganisms and their role in the pathogenesis of autoimmune diseases.


Subject(s)
Humans , Autoimmune Diseases/immunology , Autoimmunity/immunology , T-Lymphocytes, Helper-Inducer/immunology , B-Lymphocytes/immunology , Lymphocyte Activation/immunology , CD4-Positive T-Lymphocytes/immunology , Signal Transduction , Cell Differentiation , Interleukins/immunology , Th2 Cells/immunology , Interleukin-17/immunology , Th17 Cells/immunology
9.
Braz. j. med. biol. res ; 49(8): e5215, 2016. graf
Article in English | LILACS | ID: lil-787389

ABSTRACT

Angiotensin-converting enzyme (ACE) inhibitors have non-hemodynamic, pleiotropic effects on the immune response. The effects of ACE inhibitors on the production of cytokines and T-cell functions are well established. However, little is known on the effects of these medicines on humoral response to foreign antigens. In this study, we investigated the effect of enalapril treatment on ovalbumin (OVA)-specific IgG1 and IgG2c production in mice determined by ELISA. Two groups of 8-week-old C57BL/6 females mice (3–4/group) were subcutaneously immunized with OVA (10 μg/animal) in presence of Alhydrogel (1 mg/mouse) and boosted at day 21. The mice were treated with enalapril (5 mg/kg daily, po) or were left without treatment for one month. The animals were bled from the orbital plexus on days 0, 7, 14, 21, and 28 after the first immunization and the sera were stored at –20°C until usage. OVA-specific serum IgG1 and IgG2c were determined by ELISA using serum from each individual animal. The results showed that enalapril significantly increased anti-OVA serum IgG2c in the secondary response without affecting IgG1 synthesis. These data expand our understanding on the properties of enalapril on the immune response, including antibody production.


Subject(s)
Animals , Female , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Enalapril/pharmacology , Immunity, Humoral/drug effects , Immunoglobulin G/blood , Ovalbumin/immunology , Antibody Formation/drug effects , Immunoglobulin G/immunology , Mice, Inbred C57BL , Models, Animal , Th1 Cells/immunology , Th2 Cells/immunology
10.
Article in English | WPRIM | ID: wpr-155351

ABSTRACT

To determine alteration of immune responses during visceral larva migrans (VLM) caused by Toxascaris leonina at several time points, we experimentally infected mice with embryonated eggs of T. leonina and measured T-helper (Th) cell-related serial cytokine production after infection. At day 5 post infection (PI), most larvae were detected from the lungs, spleen, intestine, and muscle. Expression of thymic stromal lymphopoietin (TSLP) and CCL11 (eotaxin) showed a significant increase in most infected organs, except the intestine. However, expression of the CXCL1 (Gro-alpha) gene was most highly enhanced in the intestine at day 14 PI. Th1-related cytokine secretion of splenocytes showed increases at day 28 PI, and the level showed a decrease at day 42 PI. Th2-related cytokine secretion of splenocytes also showed an increase after infection; in particular, IL-5 level showed a significant increase at day 14 PI, and the level showed a decrease at day 28 PI. However, levels of Th17-related cytokines, IL-6 and IL-17A, showed gradual increases until day 42 PI. In conclusion, Th1, Th2, and Th17-related cytokine production might be important in immune responses against T. leonina VLM in experimental mice.


Subject(s)
Animals , Brain/parasitology , Cytokines/metabolism , Female , Gene Expression Regulation , Heart/parasitology , Interleukins/metabolism , Intestines/parasitology , Larva Migrans, Visceral/immunology , Liver/parasitology , Lung/parasitology , Mice , Mice, Inbred C57BL , Muscles/parasitology , Spleen/parasitology , Th1 Cells/immunology , Th17 Cells/immunology , Th2 Cells/immunology , Toxascaris/immunology
11.
Article in English | WPRIM | ID: wpr-118762

ABSTRACT

This study aimed to investigate the antibody responses in mice immunized with Gnathostoma spinigerum crude antigen (GsAg) incorporated with the combined adjuvant, a synthetic oligonucleotide containing unmethylated CpG motif (CpG ODN 1826) and a stable water in oil emulsion (Montanide ISA720). Mice immunized with GsAg and combined adjuvant produced all antibody classes and subclasses to GsAg except IgA. IgG2a/2b/3 but not IgG1 subclasses were enhanced by immunization with CpG ODN 1826 when compared with the control groups immunized with non-CpG ODN and Montanide ISA or only with Montanide ISA, suggesting a biased induction of a Th1-type response by CpG ODN. After challenge infection with live G. spinigerum larvae, the levels of IgG2a/2b/3 antibody subclasses decreased immediately and continuously, while the IgG1 subclass remained at high levels. This also corresponded to a continuous decrease of the IgG2a/IgG1 ratio after infection. Only IgM and IgG1 antibodies, but not IgG2a/2b/3, were significantly produced in adjuvant control groups after infection. These findings suggest that G. spinigerum infection potently induces a Th2-type biased response.


Subject(s)
Adjuvants, Immunologic/administration & dosage , Animals , Antibodies, Helminth/blood , Antigens, Helminth/administration & dosage , Gnathostoma/immunology , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Mannitol/administration & dosage , Mice , Oleic Acids/administration & dosage , Oligodeoxyribonucleotides/administration & dosage , Th1 Cells/immunology , Th2 Cells/immunology
12.
Egyptian Journal of Hospital Medicine [The]. 2011; 42 (January): 73-84
in English | IMEMR | ID: emr-162123

ABSTRACT

The role of T-Helper 2 [Th2] cells in the pathogenesis of allergy and asthma has been well described. However, the immunologic mechanisms that down modulate and protect against the development of these disorders are poorly characterized. A spectrum of CD4+ T cells, including, FOXP3-positive CD4+CD25+ T regulatory cells [Tregs] might play a critical role in regulating these diseases. To investigate the role of CD4+CD25high FoxP3 Tregs in the pathogenesis of pediatric asthma. The study included 24 asthmatic children, 12 had mild intermittent asthma and 12 were of severe persistent asthma . In addition, 12 healthy subjects were used as controls. All patients were subjected to clinical examination and laboratory investigations including complete blood count with differential leucocytic and absolute eosinophilic count, serum total IgE level by ELIZA and flow cytometry was used to study the frequency of Tregs in peripheral blood lymphocytes of all studied groups using specific markers: cell-surface CD25 and CD4 expression and cytoplasmic FoxP3 expression. It was noticed a significant decrease in CD4+CD25+ % and CD4+CD25 high % in both mild intermittent cases and severe persistent asthmatic patients when compared to healthy controls. FoxP3 expression in Tregs was significantly lower in CD4+CD25high T-cells of mild asthmatic patients when compared to control group. While the FoxP3 expression in Tregs was non- significantly lower in CD4+CD25high T-cells of severe asthmatic patients .Tregs cells % was correlated significantly with mild asthma .While it did not show correlation with severe asthma . An inverse correlation between FoxP3 protein expression was revealed within CD4+CD25high T-cells and total serum IgE when analyzed for all subjects. However, when correlation analysis was performed in each studied group separately, no significant correlation was found between FoxP3 expression and total serum IgE levels and there was no correlation between FoxP3 protein expressions within CD4+CD25high T-cells and eosinophilic count was noticed. The correlation of CD4+CD25high FoxP3 Tregs with asthma pathogenesis indicates that it is important to evaluate Tregs in allergic asthmatic children. Greater understanding of the molecular and immunological mechanisms underlying the CD4+CD25high FoxP3 Tregs might contribute the development of treatment modalities to influence disease processes of bronchial asthma in children as a future therapeutic target


Subject(s)
Humans , Female , Male , Child, Preschool , Child , Forkhead Transcription Factors , Th2 Cells/immunology , CD4 Antigens , T-Lymphocytes, Regulatory , Immunoglobulin E , Enzyme-Linked Immunosorbent Assay , Child , Pediatrics
13.
Article in English | WPRIM | ID: wpr-182110

ABSTRACT

In order to get a better understanding of the role of protease-activated receptor 2 (PAR2) in type 2 helper T (Th2) cell responses against Trichinella spiralis infection, we analyzed Th2 responses in T. spiralis-infected PAR2 knockout (KO) mice. The levels of the Th2 cell-secreted cytokines, IL-4, IL-5, and IL-13 were markedly reduced in the PAR2 KO mice as compared to the wild type mice following infection with T. spiralis. The serum levels of parasite-specific IgE increased significantly in the wild type mice as the result of T. spiralis infection, but this level was not significantly increased in PAR2 KO mice. The expression level of thymic stromal lymphopoietin, IL-25, and eotaxin gene (the genes were recently known as Th2 response initiators) of mouse intestinal epithelial cells were increased as the result of treatment with T. spiralis excretory-secretory proteins. However, the expression of these chemokine genes was inhibited by protease inhibitor treatments. In conclusion, PAR2 might involve in Th2 responses against T. spiralis infection.


Subject(s)
Animals , Antibodies, Helminth/blood , Chemokine CCL11/biosynthesis , Cytokines/biosynthesis , Female , Gene Expression Profiling , Immunoglobulin E/blood , Interleukin-13/metabolism , Interleukin-4/metabolism , Interleukin-5/metabolism , Interleukins/biosynthesis , Mice , Mice, Inbred C57BL , Mice, Knockout , Receptor, PAR-2/metabolism , Th2 Cells/immunology , Trichinella spiralis/immunology , Trichinellosis/immunology
14.
Article in English | WPRIM | ID: wpr-75334

ABSTRACT

Prostaglandin D2 (PGD2) is a major prostanoid, produced mainly by mast cells, in allergic diseases, including bronchial asthma. PGD2-induced vasodilatation and increased permeability are well-known classical effects that may be involved in allergic inflammation. Recently, novel functions of PGD2 have been identified. To date, D prostanoid receptor (DP) and chemoattractant receptor homologous molecule expressed on TH2 cells (CRTH2) have been shown to be major PGD2-related receptors. These two receptors have pivotal roles mediating allergic diseases by regulating the functions of various cell types, such as TH2 cells, eosinophils, basophils, mast cells, dendritic cells, and epithelial cells. This review will focus on the current understanding of the roles of PGD2 and its metabolites in TH2 inflammation and the pathogenesis of bronchial asthma.


Subject(s)
Asthma/etiology , Basophils/physiology , Eosinophils/physiology , Humans , Mast Cells/physiology , Prostaglandin D2/physiology , Receptors, Immunologic/physiology , Receptors, Prostaglandin/physiology , Th2 Cells/immunology
15.
Article in English | WPRIM | ID: wpr-48420

ABSTRACT

CD4+ T lymphocytes play a major role in regulation of adaptive immunity. Upon activation, naive T cells differentiate into different functional subsets. In addition to the classical Th1 and Th2 cells, several novel effector T cell subsets have been recently identified, including Th17 cells. There has been rapid progress in characterizing the development and function of Th17 cells. Here I summarize and discuss on the genetic controls of their differentiation and emerging evidence on their plasticity. This information may benefit understanding and treating immune diseases.


Subject(s)
Animals , CD4-Positive T-Lymphocytes/cytology , Cell Differentiation , Cell Lineage , Cytokines/genetics , Epigenesis, Genetic , Gene Expression Regulation , Humans , Interleukin-17/immunology , T-Lymphocytes, Regulatory , Th1 Cells/immunology , Th17 Cells/immunology , Th2 Cells/immunology , Transcription Factors/genetics , Transcription, Genetic
16.
Article in English | WPRIM | ID: wpr-48416

ABSTRACT

Mast cells are well recognized as key cells in allergic reactions, such as asthma and allergic airway diseases. However, the effects of mast cells and TNF-alpha on T-helper type 2 (Th2) cytokine-dependent asthma are not clearly understood. Therefore, an aim of this study was to investigate the role of mast cells on Th2 cytokine-dependent airway hyperresponsiveness and inflammation. We used genetically mast cell-deficient WBB6F1/J-KitW/KitW-v (W/Wv), congenic normal WBB6F1/J-Kit+/Kit+ (+/+), and mast cell-reconstituted W/Wv mouse models of allergic asthma to investigate the role of mast cells in Th2 cytokine-dependent asthma induced by ovalbumin (OVA). And we investigated whether the intratracheal injection of TNF-alpha directly induce the expression of ICAM-1 and VCAM-1 in W/Wv mice. This study, with OVA-sensitized and OVA-challenged mice, revealed the following typical histopathologic features of allergic diseases: increased inflammatory cells of the airway, airway hyperresponsiveness, and increased levels of TNF-alpha, intercellular adhesion molecule (ICAM)-1, and vascular cellular adhesion molecule (VCAM)-1. However, the histopathologic features and levels of ICAM-1 and VCAM-1 proteins in W/Wv mice after OVA challenges were significantly inhibited. Moreover, mast cell-reconstituted W/Wv mice showed restoration of histopathologic features and recovery of ICAM-1 and VCAM-1 protein levels that were similar to those found in +/+ mice. Intratracheal administration of TNF-alpha resulted in increased ICAM-1 and VCAM-1 protein levels in W/Wv mice. These results suggest that mast cells play a key role in a Th2 cytokine-dependent asthma model through production of adhesion molecules, including ICAM-1 and VCAM-1, by liberation of TNF-alpha.


Subject(s)
Animals , Asthma/immunology , Blotting, Western , Bronchoalveolar Lavage Fluid/immunology , Cytokines/immunology , Intercellular Adhesion Molecule-1/biosynthesis , Lung/immunology , Mast Cells/immunology , Mice , Ovalbumin , Th2 Cells/immunology , Tumor Necrosis Factor-alpha/metabolism , Vascular Cell Adhesion Molecule-1/biosynthesis
17.
Article in English | WPRIM | ID: wpr-200112

ABSTRACT

IL-4 and IL-13 are closely related cytokines that are produced by Th2 cells. However, IL-4 and IL-13 have different effects on the development of asthma phenotypes. Here, we evaluated downstream molecular mechanisms involved in the development of Th2 type asthma phenotypes. A murine model of Th2 asthma was used that involved intraperitoneal sensitization with an allergen (ovalbumin) plus alum and then challenge with ovalbumin alone. Asthma phenotypes, including airway-hyperresponsiveness (AHR), lung inflammation, and immunologic parameters were evaluated after allergen challenge in mice deficient in candidate genes. The present study showed that methacholine AHR and lung inflammation developed in allergen-challenged IL-4-deficient mice but not in allergen-challenged IL-13-deficient mice. In addition, the production of OVA-specific IgG2a and IFN-gamma-inducible protein (IP)-10 was also impaired in the absence of IL-13, but not of IL-4. Lung-targeted IFN-gamma over-expression in the airways enhanced methacholine AHR and non-eosinophilic inflammation; in addition, these asthma phenotypes were impaired in allergen-challenged IFN-gamma-deficient mice. Moreover, AHR, non-eosinophilic inflammation, and IFN-gamma expression were impaired in allergen-challenged IL-12Rbeta2- and STAT4-deficient mice; however, AHR and non-eosinophilic inflammation were not impaired in allergen-challenged IL-4Ralpha-deficient mice, and these phenomena were accompanied by the enhanced expression of IL-12 and IFN-gamma. The present data suggest that IL-13-mediated asthma phenotypes, such as AHR and non-eosinophilic inflammation, in the Th2 type asthma are dependent on the IL-12-STAT4-IFN-gamma axis, and that these asthma phenotypes are independent of IL-4Ralpha-mediated signaling.


Subject(s)
Allergens/immunology , Animals , Asthma/complications , Bronchial Hyperreactivity/complications , Disease Models, Animal , Interferon-gamma/immunology , Interleukin-12/immunology , Interleukin-12 Receptor beta 2 Subunit/metabolism , Interleukin-13/deficiency , Interleukin-4/deficiency , Methacholine Chloride , Mice , Mice, Transgenic , Models, Immunological , Organ Specificity , Pneumonia/complications , Receptors, Cell Surface/metabolism , STAT4 Transcription Factor/metabolism , Signal Transduction/immunology , Th2 Cells/immunology
18.
Article in English | WPRIM | ID: wpr-160875

ABSTRACT

Historically, German chamomile (GC) oil has been used for treatment of skin disorders. BALB/c mice were sensitized twice a week with 100 microL of 1% 2,4-dinitrochlorobenzene (DNCB) and challenged twice the following week with 100 microliter of 0.2% DNCB for atopic dermatitis induction. Thereafter, 3% GC oil was applied daily (70 microliter, 6 times week) on the dorsal skin for 4 weeks. Saline or jojoba oil was used for the control mice. Blood was collected after second DNCB challenge, and at 2 and 4 weeks after initiating oil application. Serum IgE levels were significantly lowered in the GC oil application group at the end of the 4-week application period. The GC oil application for 4 weeks resulted in reduction in serum IgG1 level compared with that after 2-week application. The GC oil application group showed a significantly lower serum histamine level than the control group 2 weeks after oil application. Scratching frequency of the GC oil application group was significantly lower than either control groups. This study is to demonstrate GC oil's immunoregulatory potential for alleviating atopic dermatitis through influencing of Th2 cell activation.


Subject(s)
Animals , Behavior, Animal/drug effects , Chamomile/immunology , Dermatitis, Atopic/drug therapy , Disease Models, Animal , Histamine/blood , Immunoglobulin E/blood , Immunoglobulin G/blood , Interleukin-4/analysis , Male , Matricaria/immunology , Mice , Mice, Inbred BALB C , Phytotherapy/methods , Specific Pathogen-Free Organisms , Th2 Cells/immunology
19.
Article in English | IMSEAR | ID: sea-135950

ABSTRACT

Background & objectives: Human cystic echinococcosis (CE), caused by Echinococcus granulosus, is one of the most important and widespread parasitic zoonoses. T helper cell-2 (Th2) dominated immunity in CE is associated with increased susceptibility to the disease, while T helper cell-1 (Th1) cell activation is assumed to induce protective immunity. Hence, in order to investigate in vivo Th2 cell activation and serum complement levels, the present study was aimed to detect serum levels of specific IgG, IgE, interleukin (IL)-4, IL-10, C3c and C4 in confirmed CE patients. Methods: Specific IgG levels in serum was measured by enzyme linked immunosorbent assay using recombinant E. granulosus antigen-B/2 (RecEg-AgB/2) and serum IgE, IL-4, IL-10, C3c and C4 were quantified by nephelometry in 45 surgically confirmed patients with CE, and 10 healthy controls. Results: Specific IgG (P<0.0001), IgE (P<0.05), IL-4 (P=0.0197) and IL-10 (P<0.01) levels were significantly elevated in CE cases compared to healthy controls. IL-4 could be detected in 34 patients (75.55%) and six controls (60%) in a low concentration. The IgE concentration was elevated (>120 U/ml) in 36 (80%) cases of CE and in one healthy control. Interpretation & conclusion: Our results showed higher C3c and C4 levels in CE patients than healthy controls. No significant association was found between IgE concentrations and cytokine levels. The results of this study point to a cytokine profile suggestive of Th2 cell dominance in vivo in CE.


Subject(s)
Adult , Aged , Animals , Antibodies, Helminth/blood , Case-Control Studies , Complement System Proteins/metabolism , Cytokines/blood , Echinococcosis/immunology , Echinococcus granulosus/immunology , Female , Humans , Male , Middle Aged , Th2 Cells/immunology , Young Adult
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