Smad3 -signalling and Th2 cytokines in normal mouse airways and in a mouse model of asthma.
Smad3 -signalling and Th2 cytokines in normal mouse airways and in a mouse model of asthma.
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DOI：
10.7150/ijbs.3.477
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发表时间：
2007-11-24
影响因子：
9.2
通讯作者：
Wolff HJ
中科院分区：
文献类型：
--
作者：
Anthoni M;Wang G;Leino MS;Lauerma AI;Alenius HT;Wolff HJ
本研究探讨了Smad 3信号转导在正常肺和哮喘小鼠模型中对T-helper 2（Th 2）细胞因子稳态的作用。我们使用了Smad 3缺陷的小鼠，这是TGF-β和其他相关细胞因子的主要信号转导途径的中心部分，以及用卵清蛋白（OVA）作为抗原的过敏性哮喘小鼠模型。与野生型小鼠相比，未处理的Smad 3-/-小鼠在肺组织和支气管肺泡灌洗液（BAL）中表现出显著增加的促炎细胞因子和IL-4以及Th 2相关转录因子加塔-3水平。在哮喘模型中，与野生型（WT）小鼠相比，Smad 3-/-小鼠中过敏原暴露后的粘蛋白分泌和气道高反应性（AHR）显著增加。Smad 3-/-小鼠的IL-4水平与WT小鼠相似，但与相应的WT小鼠相比，OVA致敏的Smad 3-/-小鼠气道中的IL-13水平降低。结果表明，在正常状态下缺乏Smad 3依赖性信号传导将导致加塔-3水平的增加，并且因此IL-4水平增加。然而，Smad 3的缺乏似乎也抑制了一些细胞因子的表达，特别是IL-13。我们的研究结果还表明，在炎症状态下，TGF-β或相关细胞因子的功能是平衡IL-4的作用，而不是严格调节其表达。
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.