高迁移率族蛋白1调控炎症反应机制的研究进展

Research progress in mechanism of high mobility group box 1 regulating inflammatory response

机体受到感染、外伤后发生以防御反应为主的炎症应答,高迁移率族蛋白1(HMGB1)为重要的“炎症介质”,广泛存在于各种细胞中介导炎症应答。然而HMGB1在炎症中的生物学功能因蛋白修饰种类和细胞中定位的不同而呈现差异,其在细胞核中发生赖氨酸残基乙酰化、赖氨酸残基甲基化、半胱氨酸残基氧化、丝氨酸残基磷酸化、天冬酰胺残基糖基化、腺苷二磷酸-核糖基化及赖氨酸残基乳酸化修饰,蛋白修饰后由细胞核迁移到细胞质,并释放到细胞外。细胞外游离的HMGB1可与晚期糖基化终产物受体、Toll样受体结合,活化细胞和调控炎症应答。笔者从HMGB1翻译后修饰、释放、生物学作用及结合受体等方面,就其调控炎症反应机制的研究进展进行综述,为寻找炎症干预靶标提供理论依据。

Inflammatory reaction dominated by defense response will arise against infection and trauma.As an important proinflammatory cytokine,high mobility group box 1(HMGB1)is widely expressed in all nuclear cells to mediate the inflammatory response.However,the biological functions of HMGB1 in inflammation vary depending on the type of HMGB1 protein modification and the localization in the cell.HMGB1 protein will be modified as acetylation of lysine residues,methylation of lysine residues,oxidation of cysteine residues,phosphorylation of serine residues,glycosylation of asparagine residues,adenosine diphosphate-ribosylation and lactylation of the protein in the nucleus,migrate from the nucleus to the cytoplasm,and release into the extracellular compartment.Extracellular HMGB1 can bind to receptors for advanced glycation end products(RAGE)and Toll-like receptors,activate cells and regulate inflammatory responses.The authors review the research progress in regulatory mechanism of HMGB1 in inflammation response from aspects of its post-translational modifications,releases,biological roles and binding receptors,hoping to provide theoretical basis for finding the targets of inflammation intervention.