期刊
GUT
卷 60, 期 11, 页码 1494-1505出版社
B M J PUBLISHING GROUP
DOI: 10.1136/gut.2010.221879
关键词
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资金
- Ministry of Culture and Science of Japan [18590677]
- Kato Memorial Trust for Nambyo Research
- Shimizu Foundation for the Promotion of Immunology Research
- Japan Foundation for Applied Enzymology
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [16017240, 16017249, 17013051, 17659212, 18012029]
- JSPS [15209024, 18209027]
- Ministry of Health, Labor, and Welfare, Japan [nano005]
- Grants-in-Aid for Scientific Research [15209024, 23590361, 18590677, 23590940, 18209027, 17013051, 21229009, 17659212, 21590810, 16017249] Funding Source: KAKEN
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.
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