STAT6-mediated signaling in Th2-dependent allergic asthma: critical role for the development of eosinophilia, airway hyper-responsiveness and mucus hypersecretion, distinct from its role in Th2 differentiation
| Autor: | Takafumi Jinushi, Takashi Nishimura, Akihiko Hoshino, Yoshitaka Tanaka, Kenji Chamoto, Shigeru Ashino, Tsuguhide Takeshima, Takanobu Sakurai, Hiroaki Ikeda, Yumiko Asakura, Yasuo Mita, Akiko Takaoka, Takashi Teramura, Shiro Nakaike, Takemasa Tsuji, Junko Matsuzaki |
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| Rok vydání: | 2004 |
| Předmět: |
Chemokine CCL11
Eotaxin medicine.medical_specialty Chemokine Allergy Ovalbumin Immunology Mice Th2 Cells Internal medicine Eosinophilia parasitic diseases Hypersensitivity Animals Immunology and Allergy Medicine Lung Pulmonary Eosinophilia Administration Intranasal integumentary system medicine.diagnostic_test biology business.industry Cell Differentiation General Medicine respiratory system medicine.disease Mucus Asthma Recombinant Proteins respiratory tract diseases Bronchoalveolar lavage Endocrinology Chemokines CC Trans-Activators biology.protein Bronchial Hyperreactivity medicine.symptom STAT6 Transcription Factor business Bronchoalveolar Lavage Fluid |
| Zdroj: | International Immunology. 16:1497-1505 |
| ISSN: | 1460-2377 |
| Popis: | When wild-type BALB/c mice were transferred with OVA-specific Th2 cells followed by OVA inhalation, a severe eosinophilia, mucus hypersecretion and airway hyper-responsiveness (AHR) was induced in parallel with a marked elevation of IL-4, IL-5 and IL-13 levels in bronchoalveolar lavage fluid (BALF). However, neither eosinophilia, AHR nor mucus hypersecretion was induced in Th2 cell-transferred STAT6-/- mice. The failure of eosinophilia was not due to the defect of Th2 cytokine production in BALF of STAT6-/- mice transferred with Th2 cells, but because of the defect of STAT6-dependent eotaxin production. Indeed, intranasal administration of eotaxin reconstituted pulmonary eosinophilia but not AHR and mucus hypersecretion in OVA-inhalated STAT6-/- mice. These results initially provided direct evidence that STAT6-dependent eotaxin production is essential for pulmonary eosinophilia. We also dissociated the role of STAT6 for eosinophilia from that for AHR and mucus hypersecretion. Thus, STAT6 also plays a critical role at late phase of Th2-dependent allergy induction. |
| Databáze: | OpenAIRE |
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