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骨膜蛋白与变应性炎症

Periostin in allergic inflammation.

作者信息

Izuhara Kenji, Arima Kazuhiko, Ohta Shoichiro, Suzuki Shoichi, Inamitsu Masako, Yamamoto Ken-ichi

机构信息

Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga, Japan.

Department of Laboratory Medicine, Saga Medical School, Saga, Japan.

出版信息

Allergol Int. 2014 Jun;63(2):143-51. doi: 10.2332/allergolint.13-RAI-0663. Epub 2014 Mar 25.

Abstract

Periostin, an extracellular matrix protein belonging to the fasciclin family, has been shown to play a critical role in the process of remodeling during tissue/organ development or repair. Periostin functions as a matricellular protein in cell activation by binding to their receptors on cell surface, thereby exerting its biological activities. After we found that periostin is a downstream molecule of interleukin (IL)-4 and IL-13, signature cytokines of type 2 immune responses, we showed that periostin is a component of subepithelial fibrosis in bronchial asthma, the first formal proof that periostin is involved in allergic inflammation. Subsequently, a great deal of evidence has accumulated demonstrating the significance of periostin in allergic inflammation. It is of note that in skin tissues, periostin is critical for amplification and persistence of allergic inflammation by communicating between fibroblasts and keratinocytes. Furthermore, periostin has been applied to development of novel diagnostics or therapeutic agents for allergic diseases. Serum periostin can reflect local production of periostin in inflamed lesions induced by Th2-type immune responses and also can predict the efficacy of Th2 antagonists against bronchial asthma. Blocking the interaction between periostin and its receptor, αv integrin, or down-regulating the periostin expression shows improvement of periostin-induced inflammation in mouse models or in in vitro systems. It is hoped that diagnostics or therapeutic agents targeting periostin will be of practical use in the near future.

摘要

骨膜蛋白是一种属于成束蛋白家族的细胞外基质蛋白,已被证明在组织/器官发育或修复过程中的重塑过程中起关键作用。骨膜蛋白作为一种基质细胞蛋白,通过与细胞表面的受体结合来激活细胞,从而发挥其生物学活性。在我们发现骨膜蛋白是2型免疫反应的标志性细胞因子白细胞介素(IL)-4和IL-13的下游分子后,我们证明骨膜蛋白是支气管哮喘上皮下纤维化的一个组成部分,这是骨膜蛋白参与过敏性炎症的首个正式证据。随后,大量证据积累,证明了骨膜蛋白在过敏性炎症中的重要性。值得注意的是,在皮肤组织中,骨膜蛋白通过成纤维细胞和角质形成细胞之间的通讯,对过敏性炎症的放大和持续至关重要。此外,骨膜蛋白已被应用于过敏性疾病新型诊断方法或治疗药物的开发。血清骨膜蛋白可以反映由Th2型免疫反应诱导的炎症病变中骨膜蛋白的局部产生情况,还可以预测Th2拮抗剂对支气管哮喘的疗效。在小鼠模型或体外系统中,阻断骨膜蛋白与其受体αv整合素之间的相互作用,或下调骨膜蛋白的表达,可改善骨膜蛋白诱导的炎症。人们希望,针对骨膜蛋白的诊断方法或治疗药物在不久的将来将具有实际应用价值。

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