酰基羧酸水解酶在疾病中的作用及机制研究进展

Research progress in the role and mechanism of acyloxyacyl hydrolase in diseases

脂多糖(lipopolysaccharide,LPS)是革兰阴性菌细胞壁外壁的重要组成部分,能够引起机体强烈的免疫炎症反应。酰基羧酸水解酶(acyloxyacyl hydrolase,AOAH)是一种高度保守的宿主脂肪酶,在中性粒细胞、巨噬细胞和近端肾小管上皮细胞等多种细胞中表达。AOAH能够选择性地去除革兰阴性菌LPS脂质A的二级酰基链从而灭活LPS,减轻感染所致的炎症与组织损伤,促进机体脱离免疫耐受状态,恢复正常的免疫应答能力,在感染性疾病中发挥重要作用。此外,多项体内或体外实验证明,AOAH还具有磷脂酶、溶血磷脂酶、二酰甘油脂肪酶等多种酶活性。越来越多的研究表明,除感染性疾病外,AOAH还在过敏性哮喘、银屑病、慢性盆腔疼痛等自身免疫性疾病或慢性炎症性疾病等非感染性疾病中扮演重要角色。不仅如此,上海交通大学医学院附属第九人民医院肾脏内科丁峰课题组研究发现,AOAH可以抑制近端肾小管上皮细胞CD74通路,减轻肾脏纤维化。基于AOAH在疾病中展现出越来越多的作用,该文对AOAH的来源、结构及其在疾病中的作用和可能的机制进行综述,以期为未来研究AOAH在疾病中的功能提供参考,并为阐明疾病的发病机制及寻找治疗靶点提供新的思路。

Lipopolysaccharide(LPS)is an essential component of the outer wall of gram-negative bacteria and can induce a strong inflammatory response in the body.Acyloxyacyl hydrolase(AOAH)is a highly conserved host lipase expressed in a variety of cells,including neutrophils,macrophages and proximal tubular epithelial cells.AOAH can inactivate LPS by selectively removing the secondary acyl chains from the lipid A moiety of gram-negative bacterial LPS,which alleviates inflammation and tissue damage,promotes the recovery from the immune tolerance and regains normal responsiveness.It plays an essential role in host defenses against infection.Moreover,AOAH has been shown invivo and invitro for a variety of enzymatic activities including phospholipase,lysophospholipase and diacylglycerol lipase.Researches increasingly show that AOAH plays a critical role in various noninfectious diseases such as allergic asthma,psoriasis,chronic pelvic pain and other autoimmune diseases and chronic inflammatory diseases in addition to infections.Besides,DING Feng Research Group,Department of Nephrology,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine found that AOAH was capable of attenuating renal fibrosis via proximal renal tubular epithelial cells CD74 signaling pathway.Given the increasingly diverse role of AOAH in diseases,this article reviews its sources,structure,effects and possible mechanisms in diseases in order to provide reference for future research on its roles in diseases and new lines of investigation into disease pathogenesis and novel therapeutic targets.