SR-PSOX/CXCL16 plays a critical role in the progression of colonic inflammation
SR-PSOX/CXCL16 plays a critical role in the progression of colonic inflammation
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DOI：
10.1136/gut.2010.221879
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发表时间：
2011-11-01
期刊：
影响因子：
24.5
通讯作者：
Chiba, Tsutomu
中科院分区：
文献类型：
--
作者：
Uza, Norimitsu;Nakase, Hiroshi;Chiba, Tsutomu
背景和目的炎症性肠病(IBD)是由对未知环境抗原(如遗传易感宿主中的管腔细菌)的免疫反应失调而引发和持续的。SR-PSOX/CXCL16是一种结合磷脂酰丝氨酸和氧化脂蛋白的清道夫受体，具有吞噬活性和趋化活性。本研究旨在探讨SR-PSOX/CXCL16在IBD和实验性小鼠结肠炎中的作用。研究了SR-PSOX/CXCL16在野生型(WT)和SR-PSOX/CXCL16基因敲除(KO)小鼠巨噬细胞吞噬细菌成分和产生细胞因子中的作用。用葡聚糖硫酸钠(DSS)诱导WT和SR-PSOX/CXCL16 KO小鼠结肠炎。从临床、组织学和免疫学指标分析结肠炎。结果血清SR-PSOX/CXCL16水平与IBD患者的疾病活动性密切相关。体外实验表明，SR-PSOX/CXCL16通过产生白介素12和干扰素-γ，参与细菌抗原的吞噬和T辅助细胞免疫应答。小鼠体内实验表明，炎症结肠组织中SR-PSOX/CXCL16基因表达上调，巨噬细胞上SR-PSOX/CXCL16基因优势表达。与WT小鼠相比，SR-PSOX/CXCL16KO小鼠对结肠炎的易感性较低。结论SR-PSOX/CXCL16在结肠炎中起重要作用，有望成为IBD治疗的新靶点。
Background and aims Inflammatory bowel disease (IBD) is initiated and perpetuated by a dysregulated immune response to unknown environmental antigens such as luminal bacteria in genetically susceptible hosts. SR-PSOX/CXCL16, a scavenger receptor that binds phosphatidylserine and oxidised lipoprotein, has both phagocytic activity and chemotactic properties. The aim of this study was to investigate the role of SR-PSOX/CXCL16 in patients with IBD and experimental murine colitis.Methods The serum levels of SR-PSOX/CXCL16 were measured in patients with IBD. The roles of SR-PSOX/CXCL16 in phagocytosis of bacterial components and cytokine production by macrophages from wild-type (WT) and SR-PSOX/CXCL16 knockout (KO) mice were assessed. Colitis was induced by administering dextran sulfate sodium (DSS) to WT and SR-PSOX/CXCL16 KO mice. Colonic inflammation was analysed by clinical, histological and immunological parameters. Finally, the effect of a monoclonal antibody (mAb) to SR-PSOX/CXCL16 on DSS-induced colitis and trinitrobenzene sulfonic acid-induced colitis models was evaluated.Results Serum levels of SR-PSOX/CXCL16 correlated significantly with the disease activity of patients with IBD. Ex vivo experiments showed that SR-PSOX/CXCL16 was involved in both phagocytosis of bacterial antigens and the T helper 1 immune response through the production of interleukin 12 and interferon gamma. In vivo murine experiments demonstrated the upregulated gene expression of SR-PSOX/CXCL16 in inflamed colonic tissues and the predominant expression of SR-PSOX/CXCL16 on macrophages. SR-PSOX/CXCL16 KO mice were less susceptible to colonic inflammation than were their WT littermates. Administration of SR-PSOX/CXCL16 mAb ameliorated the condition in the two different experimental colitis models.Conclusions SR-PSOX/CXCL16 plays a critical role in colonic inflammation and could be a potential therapeutic target for patients with IBD.