SR-PSOX/CXCL16 plays a critical role in the progression of colonic inflammation.

Abstract

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 γ. 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.

• Authors: Norimitsu Uza, Hiroshi Nakase, Shuji Yamamoto, Takuya Yoshino, Yasuhiro Takeda, Satoru Ueno, Satoko Inoue, Sakae Mikami, Minoru Matsuura, Takeshi Shimaoka, Noriaki Kume, Manabu Minami, Shin Yonehara, Hiroki Ikeuchi, Tsutomu Chiba
• Journal: Gut (Gut) Vol. 60 Issue 11 Pg. 1494-505 (Nov 2011) ISSN: 1468-3288 [Electronic] England
• PMID: 21471570 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CXCL16 protein, human
• Chemokine CXCL16
• Chemokine CXCL6
• Chemokines, CXC
• Cxcl16 protein, mouse
• Cytokines
• Receptors, Scavenger
• Interleukin-12

Topics

• Adult
• Animals
• Chemokine CXCL16
• Chemokine CXCL6 (physiology)
• Chemokines, CXC (physiology)
• Colon (pathology)
• Cytokines (metabolism)
• Disease Progression
• Female
• Gene Expression (immunology)
• Humans
• Inflammatory Bowel Diseases (immunology, physiopathology)
• Interleukin-12 (biosynthesis, immunology)
• Macrophages, Peritoneal (immunology)
• Male
• Mice
• Mice, Knockout
• Mucous Membrane (cytology)
• Phagocytosis (physiology)
• Receptors, Scavenger (physiology)
• Young Adult