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几丁质和几丁质酶/几丁质酶样蛋白在炎症、组织重塑和损伤中的作用。

Role of chitin and chitinase/chitinase-like proteins in inflammation, tissue remodeling, and injury.

机构信息

Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8057, USA.

出版信息

Annu Rev Physiol. 2011;73:479-501. doi: 10.1146/annurev-physiol-012110-142250.

Abstract

The 18 glycosyl hydrolase family of chitinases is an ancient gene family that is widely expressed from prokaryotes to eukaryotes. In mammals, despite the absence of endogenous chitin, a number of chitinases and chitinase-like proteins (C/CLPs) have been identified. However, their roles have only recently begun to be elucidated. Acidic mammalian chitinase (AMCase) inhibits chitin-induced innate inflammation; augments chitin-free, allergen-induced Th2 inflammation; and mediates effector functions of IL-13. The CLPs BRP-39/YKL-40 (also termed chitinase 3-like 1) inhibit oxidant-induced lung injury, augments adaptive Th2 immunity, regulates apoptosis, stimulates alternative macrophage activation, and contributes to fibrosis and wound healing. In accord with these findings, levels of YKL-40 in the lung and serum are increased in asthma and other inflammatory and remodeling disorders and often correlate with disease severity. Our understanding of the roles of C/CLPs in inflammation, tissue remodeling, and tissue injury in health and disease is reviewed below.

摘要

18 糖苷水解酶家族的几丁质酶是一个古老的基因家族,广泛存在于原核生物到真核生物中。在哺乳动物中,尽管没有内源性几丁质,但已经鉴定出许多几丁质酶和几丁质酶样蛋白 (C/CLP)。然而,它们的作用直到最近才开始被阐明。酸性哺乳动物几丁质酶 (AMCase) 抑制几丁质诱导的先天炎症;增强无几丁质、变应原诱导的 Th2 炎症;并介导 IL-13 的效应功能。CLP BRP-39/YKL-40(也称为几丁质酶 3 样 1)抑制氧化剂诱导的肺损伤,增强适应性 Th2 免疫,调节细胞凋亡,刺激替代型巨噬细胞激活,并有助于纤维化和伤口愈合。与这些发现一致,哮喘和其他炎症和重塑障碍中肺和血清中的 YKL-40 水平升高,并且通常与疾病严重程度相关。下面综述了 C/CLP 在健康和疾病中的炎症、组织重塑和组织损伤中的作用。

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