Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
J Immunol. 2011 Apr 15;186(8):4959-66. doi: 10.4049/jimmunol.1002359. Epub 2011 Mar 14.
Periostin is a 90-kDa member of the fasciclin-containing family and functions as part of the extracellular matrix. Periostin is expressed in a variety of tissues and expression is increased in airway epithelial cells from asthmatic patients. Recent studies have implicated a role for periostin in allergic eosinophilic esophagitis. To further define a role for periostin in Th2-mediated inflammatory diseases such as asthma, we studied the development of allergic pulmonary inflammation in periostin-deficient mice. Sensitization and challenge of periostin-deficient mice with OVA resulted in increased peripheral Th2 responses compared with control mice. In the lungs, periostin deficiency resulted in increased airway resistance and significantly enhanced mucus production by goblet cells concomitant with increased expression of Gob5 and Muc5ac compared with wild type littermates. Periostin also inhibited the expression of Gob5, a putative calcium-activated chloride channel involved in the regulation of mucus production, in primary murine airway epithelial cells. Our studies suggest that periostin may be part of a negative-feedback loop regulating allergic inflammation that could be therapeutic in the treatment of atopic disease.
纤连蛋白富含蛋白 90kDa 是细胞外基质的组成部分，在多种组织中表达，在哮喘患者的气道上皮细胞中表达增加。最近的研究表明，纤连蛋白在变应性嗜酸性食管炎中起作用。为了进一步确定纤连蛋白在哮喘等 Th2 介导的炎症性疾病中的作用，我们研究了纤连蛋白缺乏小鼠的过敏性肺炎症的发展。与对照小鼠相比，OVA 致敏和激发纤连蛋白缺陷小鼠导致外周 Th2 反应增加。在肺部，纤连蛋白缺乏导致气道阻力增加，杯状细胞的粘液分泌显著增加，同时与野生型同窝仔相比，Gob5 和 Muc5ac 的表达增加。纤连蛋白还抑制了 Gob5 的表达，Gob5 是一种参与调节粘液产生的钙激活氯离子通道，在原代小鼠气道上皮细胞中。我们的研究表明，纤连蛋白可能是调节过敏炎症的负反馈环的一部分，在治疗特应性疾病方面可能具有治疗作用。
