Blanchard C, Mingler M K, McBride M, Putnam P E, Collins M H, Chang G, Stringer K, Abonia J P, Molkentin J D, Rothenberg M E
Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Mucosal Immunol. 2008 Jul;1(4):289-96. doi: 10.1038/mi.2008.15. Epub 2008 May 7.
Periostin is an extracellular matrix protein that has been primarily studied in the context of the heart, where it has been shown to promote cardiac repair and remodeling. In this study, we focused on the role of periostin in an allergic eosinophilic inflammatory disease (eosinophilic esophagitis (EE)) known to involve extensive tissue remodeling. Periostin was indeed markedly overexpressed (35-fold) in the esophagus of EE patients, particularly in the papillae, compared with control individuals. Periostin expression was downstream from transforming growth factor-beta and interleukin-13, as these cytokines were elevated in EE esophageal samples and markedly induced periostin production by primary esophageal fibroblasts (107- and 295-fold, respectively, at 10 ng ml(-1)). A functional role for periostin in eliciting esophageal eosinophilia was demonstrated, as periostin-null mice had a specific defect in allergen-induced eosinophil recruitment to the lungs and esophagus (66 and 72% decrease, respectively). Mechanistic analyses revealed that periostin increased (5.8-fold) eosinophil adhesion to fibronectin. As such, these findings extend the involvement of periostin to esophagitis and uncover a novel role for periostin in directly regulating leukocyte (eosinophil) accumulation in T helper type 2-associated mucosal inflammation in both mice and humans.
骨膜蛋白是一种细胞外基质蛋白，主要在心脏方面进行了研究，在心脏中它已被证明可促进心脏修复和重塑。在本研究中，我们聚焦于骨膜蛋白在一种已知涉及广泛组织重塑的过敏性嗜酸性粒细胞炎症性疾病（嗜酸性食管炎（EE））中的作用。与对照个体相比，骨膜蛋白在EE患者的食管中确实显著过度表达（35倍），尤其是在乳头中。骨膜蛋白的表达在转化生长因子-β和白细胞介素-13的下游，因为这些细胞因子在EE食管样本中升高，并显著诱导原代食管成纤维细胞产生骨膜蛋白（在10 ng ml(-1)时分别为107倍和295倍）。骨膜蛋白在引发食管嗜酸性粒细胞增多方面的功能作用得到了证实，因为骨膜蛋白基因敲除小鼠在变应原诱导的嗜酸性粒细胞向肺和食管募集中存在特定缺陷（分别减少66%和72%）。机制分析表明，骨膜蛋白增加了（5.8倍）嗜酸性粒细胞与纤连蛋白的黏附。因此，这些发现将骨膜蛋白的作用扩展到食管炎，并揭示了骨膜蛋白在直接调节小鼠和人类2型辅助性T细胞相关黏膜炎症中白细胞（嗜酸性粒细胞）积聚方面的新作用。
