A protective role for periostin and TGF-β in IgE-mediated allergy and airway hyperresponsiveness.
A protective role for periostin and TGF-β in IgE-mediated allergy and airway hyperresponsiveness.
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DOI：
10.1111/j.1365-2222.2011.03840.x
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发表时间：
2012-01
期刊：
影响因子：
--
通讯作者：
Fahy JV
中科院分区：
文献类型：
--
作者：
Gordon ED;Sidhu SS;Wang ZE;Woodruff PG;Yuan S;Solon MC;Conway SJ;Huang X;Locksley RM;Fahy JV
哮喘的病理生理学涉及气道中的过敏性炎症和重塑以及对胆碱能刺激的气道高反应性（AHR），但具体的潜在细胞和分子机制的许多细节仍然未知。骨膜蛋白是一种基质细胞蛋白，在皮肤和心脏损伤后的组织修复中发挥作用。最近已显示其在哮喘患者的气道上皮中上调并增加活性TGF-β。尽管人们可能期望骨膜蛋白在哮喘发病机制中发挥有害作用，但迄今为止，其在气道中的生物学作用尚不清楚。确定骨膜蛋白缺乏对吸入过敏原的气道反应的影响。在用烟曲霉抗原反复鼻内激发后，在骨膜蛋白缺陷小鼠和野生型对照中进行气道反应性、炎症和重塑的体内测量。还进行了上皮细胞来源的骨膜蛋白对鼠T细胞的影响的体外研究。令人惊讶的是，与野生型对照相比，骨膜蛋白缺陷小鼠在过敏原激发后产生了增加的AHR和血清IgE水平，而在气道重塑的两种结果（粘液化生和支气管周围纤维化）方面没有差异。这些变化与骨膜蛋白缺陷小鼠肺中TGF-β1和Foxp 3表达的降低有关。气道上皮细胞来源的骨膜素在体外以TGF-β依赖性方式诱导CD 4 + CD 25 −细胞转化为CD 25+、Foxp 3 + T细胞在吸入性变应原激发的骨膜蛋白缺陷小鼠中，变应原诱导的血清IgE和支气管高反应性增加被夸大。骨膜蛋白作为变应原诱导的反应的制动器的作用的机制可能涉及增强TGF-β诱导的T调节细胞分化。
The pathophysiology of asthma involves allergic inflammation and remodelling in the airway and airway hyperresponsiveness (AHR) to cholinergic stimuli, but many details of the specific underlying cellular and molecular mechanisms remain unknown. Periostin is a matricellular protein with roles in tissue repair following injury in both the skin and heart. It has recently been shown to be up-regulated in the airway epithelium of asthmatics and to increase active TGF-β. Though one might expect periostin to play a deleterious role in asthma pathogenesis, to date its biological role in the airway is unknown. To determine the effect of periostin deficiency on airway responses to inhaled allergen. In vivo measures of airway responsiveness, inflammation, and remodelling were made in periostin deficient mice and wild-type controls following repeated intranasal challenge with Aspergillus fumigatus antigen. In vitro studies of the effects of epithelial cell-derived periostin on murine T cells were also performed. Surprisingly, compared with wild-type controls, periostin deficient mice developed increased AHR and serum IgE levels following allergen challenge without differences in two outcomes of airway remodelling (mucus metaplasia and peribronchial fibrosis). These changes were associated with decreased expression of TGF-β1 and Foxp3 in the lungs of periostin deficient mice. Airway epithelial cell-derived periostin-induced conversion of CD4+ CD25− cells into CD25+, Foxp3+ T cells in vitro in a TGF-β dependent manner. Allergen-induced increases in serum IgE and bronchial hyperresponsiveness are exaggerated in periostin deficient mice challenged with inhaled aeroallergen. The mechanism of periostin's effect as a brake on allergen-induced responses may involve augmentation of TGF-β-induced T regulatory cell differentiation.
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影响因子：
5.3
作者：
Li, Guohong;Jin, Rong;Norris, Russell A.;Zhang, Lin;Yu, Shiyong;Wu, Fusheng;Markwald, Roger R.;Nanda, Anil;Conway, Simon J.;Smyth, Susan S.;Granger, D. Neil
通讯作者：
Granger, D. Neil
影响因子：
64.8
作者：
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3.7
作者：
Luo X;Ding Q;Wang M;Li Z;Mao K;Sun B;Pan Y;Wang Z;Zang YQ;Chen Y
通讯作者：
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DOI：
10.1152/ajplung.00521.2007
发表时间：
2009-03-01
影响因子：
4.9
作者：
Burchell, Jennifer T.;Wikstrom, Matthew E.;Turner, Debra J.
通讯作者：
Turner, Debra J.
影响因子：
4.4
作者：
Blease, K;Mehrad, B;Hogaboam, CM
通讯作者：
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