Lim Su Yin, Raftery Mark J, Goyette Jesse, Hsu Kenneth, Geczy Carolyn L
The Centre for Infection and Inflammation Research, School of Medical Sciences, University of New South Wales, Sydney, 2052, Australia.
J Leukoc Biol. 2009 Sep;86(3):577-87. doi: 10.1189/jlb.1008608.
Several S100 Ca(2+)-binding proteins undergo various post-translational modifications that may alter their intracellular and extracellular functions. S100A8 and S100A9, two members of this family, are particularly susceptible to oxidative modification. These proteins, abundantly expressed in neutrophils and activated macrophages, are associated with acute and chronic inflammatory conditions, including microbial infections, cystic fibrosis, rheumatoid arthritis, and atherosclerosis. They have diverse intracellular roles including NADPH oxidase activation and arachidonic acid transport and can be secreted via a Golgi-independent pathway to exert extracellular functions. Many pro-inflammatory functions have been described for S100A8 and S100A9, but they are also implicated in anti-inflammatory roles in wound-healing and protection against excessive oxidative tissue damage,the latter as a result of their exquisite capacity to scavenge oxidants. Similarly, their genes are induced by proinflammatory (LPS and TNF-alpha) stimuli, but induction is IL-10-dependent, and anti-inflammatory glucocorticoids induce or amplify expression. S100A8 and S100A9 were described recently as damage-associated molecular pattern molecules, which provide a novel, conceptual framework for understanding their functions. However, because of this designation, recent reviews focus solely on their pro-inflammatory functions. Here, we summarize the mounting evidence from functional and gene regulation studies that these proteins may also play protective roles. This review offers an explanation for the disparate, functional roles of S100A8 and S100A9 based on emerging data that post-translational, oxidative modifications may act as a regulatory switch.
几种S100钙结合蛋白会经历各种翻译后修饰，这些修饰可能会改变它们在细胞内和细胞外的功能。该家族的两个成员S100A8和S100A9特别容易受到氧化修饰。这些蛋白在中性粒细胞和活化的巨噬细胞中大量表达，与急性和慢性炎症状态相关，包括微生物感染、囊性纤维化、类风湿性关节炎和动脉粥样硬化。它们在细胞内具有多种作用，包括激活NADPH氧化酶和转运花生四烯酸，并且可以通过不依赖高尔基体的途径分泌以发挥细胞外功能。已经描述了S100A8和S100A9的许多促炎功能，但它们也参与伤口愈合中的抗炎作用以及防止过度的氧化组织损伤，后者是由于它们具有出色的清除氧化剂的能力。同样，它们的基因由促炎刺激（脂多糖和肿瘤坏死因子-α）诱导，但诱导是白细胞介素-10依赖性的，抗炎糖皮质激素会诱导或增强其表达。S100A8和S100A9最近被描述为损伤相关分子模式分子，这为理解它们的功能提供了一个新的概念框架。然而，由于这一命名，最近的综述仅关注它们的促炎功能。在这里，我们总结了功能和基因调控研究中越来越多的证据，表明这些蛋白也可能发挥保护作用。这篇综述基于新出现的数据，即翻译后氧化修饰可能作为一种调节开关，对S100A8和S100A9不同的功能作用做出了解释。
