title: Smad3 -signalling and Th2 cytokines in normal mouse airways and in a mouse model of asthma.
abstract: 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.
authors: Unit of Excellence for Immunotoxicology, Finnish Institute of Occupational Health, Helsinki, Finland.
authors: Minna
authors: M
authors: Anthoni
authors: Guoying
authors: G
authors: Wang
authors: Marina S
authors: MS
authors: Leino
authors: Antti I
authors: AI
authors: Lauerma
authors: Harri T
authors: HT
authors: Alenius
authors: Henrik J
authors: HJ
authors: Wolff
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D017353:Gene Deletion; D006706:Homeostasis / Q000502:physiology; D007249:Inflammation / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction / Q000502:physiology; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*
chemical_list: D016207:Cytokines; D051900:Smad3 Protein; C497791:Smad3 protein, mouse