title: SR-PSOX/CXCL16 plays a critical role in the progression of colonic inflammation.
abstract: OBJECTIVE
  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.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Norimitsu
authors.initials: N
authors.lastname: Uza
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakase
authors.forename: Shuji
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Takuya
authors.initials: T
authors.lastname: Yoshino
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takeda
authors.forename: Satoru
authors.initials: S
authors.lastname: Ueno
authors.forename: Satoko
authors.initials: S
authors.lastname: Inoue
authors.forename: Sakae
authors.initials: S
authors.lastname: Mikami
authors.forename: Minoru
authors.initials: M
authors.lastname: Matsuura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shimaoka
authors.forename: Noriaki
authors.initials: N
authors.lastname: Kume
authors.forename: Manabu
authors.initials: M
authors.lastname: Minami
authors.forename: Shin
authors.initials: S
authors.lastname: Yonehara
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ikeuchi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Chiba
mesh_terms: D000328:Adult; D000818:Animals; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6 / Q000502:physiology*; D019743:Chemokines, CXC / Q000502:physiology*; D003106:Colon / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000503:physiopathology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009092:Mucous Membrane / Q000166:cytology; D010587:Phagocytosis / Q000502:physiology; D051116:Receptors, Scavenger / Q000502:physiology*; D055815:Young Adult
chemical_list: C423727:CXCL16 protein, human; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; D019743:Chemokines, CXC; C498926:Cxcl16 protein, mouse; D016207:Cytokines; D051116:Receptors, Scavenger; D018664:Interleukin-12