| First Author | Anthoni M | Year | 2007 |
| Journal | Int J Biol Sci | Volume | 3 |
| Issue | 7 | Pages | 477-85 |
| PubMed ID | 18071588 | Mgi Jnum | J:161108 |
| Mgi Id | MGI:4457245 | Doi | 10.7150/ijbs.3.477 |
| Citation | Anthoni M, et al. (2007) Smad3 -signalling and Th2 cytokines in normal mouse airways and in a mouse model of asthma. Int J Biol Sci 3(7):477-85 |
| abstractText | 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-beta 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-beta or related cytokines functions to counterbalance the effects of IL-4 rather than to critically regulate its expression. |
