YM-341619 suppresses the differentiation of spleen T cells into Th2 cells in vitro, eosinophilia, and airway hyperresponsiveness in rat allergic models
| Autor: | Keiko Ohga, Sadao Kuromitsu, Yasuaki Shimizu, Mako Numazaki, Shinya Nagashima, Ryuichi Takezawa, Jun Ishikawa |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
medicine.medical_specialty medicine.medical_treatment Morpholines T-Lymphocytes GATA3 Transcription Factor Immunoglobulin E Interleukin 21 Interferon-gamma Mice Th2 Cells Internal medicine Rats Inbred BN Eosinophilia medicine Animals Rats Wistar Promoter Regions Genetic Interleukin 4 Pharmacology biology Dose-Response Relationship Drug business.industry Cell Differentiation T lymphocyte Eosinophil Asthma Rats Mice Inbred C57BL Ovalbumin medicine.anatomical_structure Cytokine Endocrinology Pyrimidines biology.protein Female Interleukin-4 Antibody Bronchial Hyperreactivity business STAT6 Transcription Factor Spleen |
| Zdroj: | European journal of pharmacology. 590(1-3) |
| ISSN: | 0014-2999 |
| Popis: | T helper (Th) 2 cells play a central role in the pathogenesis of allergic diseases such as allergic asthma, atopic dermatitis, and allergic rhinitis. We have found that YM-341619 hydrochloride, which suppressed IL-4-induced STAT6-dependent reporter gene expression, inhibited the differentiation of mouse spleen T cells into Th2 cells in vitro. YM-341619 suppressed the production of IL-4 and the expression of GATA-3 mRNA, a Th2 transcription factor, in T cells cultured with anti-CD3 antibody and anti-CD28 antibody in the presence of IL-4. In contrast, the production of IFN-gamma and the expression of T-bet mRNA, a Th1 transcription factor, in T cells cultured with anti-CD3 antibody in the presence of IL-12, were not effected by YM-341619. Orally administered YM-341619 (0.003-0.03 mg/kg) reduced the plasma IgE level of DNP-Ascaris-sensitized rats, but not the IgG(2a) level. YM-341619 suppressed IL-4 and IL-13 production in the splenocytes of these DNP-Ascaris-sensitized rats without augmenting IFN-gamma production. YM-341619 also dose-dependently suppressed eosinophil accumulation in the lung (0.003-3 mg/kg, p.o.) and airway hyperresponsiveness (0.3-3 mg/kg, p.o.) induced by repeated exposure to ovalbumin in ovalbumin-sensitized rats. These results suggest that YM-341619 has the ability to suppress allergen-induced Th2 responses by selectively inhibiting the differentiation of CD4(+) T cells into the Th2 subset. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect