| Autor: |
Minna Anthoni, Guoying Wang, Marina S. Leino, Antti I. Lauerma, Harri T. Alenius, Henrik J. Wolff |
| Jazyk: |
angličtina |
| Rok vydání: |
2007 |
| Předmět: |
|
| Zdroj: |
International Journal of Biological Sciences, Vol 3, Iss 7, Pp 477-485 (2007) |
| Druh dokumentu: |
article |
| ISSN: |
1449-2288 |
| Popis: |
This study investigates the role of Smad3 signalling for the T-helper2 (Th2) cytokine homeostasis in normal lungs and in a mouse model of asthma. We used mice deficient for Smad3, a central part of the major signal transduction pathway for TGF-β and other related cytokines, and a mouse model for allergic asthma with ovalbumin (OVA) as the antigen. Compared to wild type mice, naive (unmanipulated) Smad3-/- mice exhibited significantly increased levels of proinflammatory cytokines and IL-4 as well as the Th2 associated transcription factor GATA-3 in the lung tissue and bronchoalveolar lavage (BAL). In the asthma model, mucin secretion and airway hyperresponsiveness (AHR) after allergen exposure was significantly increased in the Smad3-/- mice as compared to wild type (WT) mice. IL-4 levels in Smad3-/- were similar to those encountered in WT mice but IL-13 levels were decreased in the airways of OVA sensitized Smad3-/- mice compared to corresponding WT mice. The results indicate that a lack of Smad3 dependent signalling in the normal state will lead to an increase in the GATA-3 levels and as a result of this the levels of IL-4 increase. However, the lack of Smad3 also seems to inhibit expression of some cytokines, especially IL-13. Our results also indicate that in the inflammatory state TGF-β or related cytokines functions to counterbalance the effects of IL-4 rather than to critically regulate its expression. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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