title: IL-10/microRNA-155/SHIP-1 signaling pathway is crucial for commensal bacteria induced spontaneous colitis.
abstract: Interleukin 10 (IL-10) microRNA-155 (miR-155)/Src homology 2 domain-containing inositol 5-phosphatase 1 (SHIP-1) signaling pathway plays an important role in maintaining immune homeostasis. We aimed to determine and characterize the changes induced by commensal bacteria on the IL-10/miR-155/SHIP-1 signaling pathway, as well as the potential therapeutic effects of anti-miR-155 on colitis in IL-10 deficient (IL-10(-)/(-)) mice. Age- and sex-matched C57BL/6 IL-10(-)/(-) and wild type mice were transferred from a germ-free environment to a specific pathogen free condition. Part of IL-10(-)/(-) mice were then treated with anti-miR-155. IL-10/miR-155/SHIP-1 signaling pathway was evaluated and the therapeutic effects of anti-miR-155 treatment on colitis in IL-10(-)/(-) mice was assessed. The expression and the relationship of IL-10, miR-155, and SHIP-1 were also measured in patients with active Crohn's colitis. IL-10/miR-155/SHIP-1 signaling pathway was activated in IL-10(-)/(-) mice transferring from a germ-free environment to a specific pathogen free condition. Anti-miR-155 treatment significantly ameliorated the severity of colitis in IL-10(-)/(-) mice. Additionally, administration of anti-miR-155 was associated with a restoration of SHIP-1 signaling pathway. The relationship of IL-10, miR-155, and SHIP-1 was confirmed in human study using samples from patients with active Crohn's colitis. IL-10/miR-155/SHIP-1 pathways play a critical role in commensal bacteria induced colitis and miR-155 may be a potential therapeutic target for human inflammatory bowel disease.
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, No. 121 Jiangjiayuan Road, Nanjing, PR China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, PR China. Electronic address: juwiming@nju.edu.cn.
authors.forename: Weiming
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, PR China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Gong
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, PR China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, PR China.
authors.forename: Feilong
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, PR China.
authors.forename: Lili
authors.initials: L
authors.lastname: Gu
authors.affiliation: Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, PR China.
authors.forename: Jieshou
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D003092:Colitis / Q000209:etiology / Q000276:immunology / Q000378:metabolism* / Q000628:therapy; D003106:Colon / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D003424:Crohn Disease / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D064806:Dysbiosis / Q000382:microbiology / Q000503:physiopathology; D005260:Female; D005856:Germ-Free Life; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D013047:Specific Pathogen-Free Organisms; D015854:Up-Regulation
chemical_list: C508609:IL10 protein, human; C556062:IL10 protein, mouse; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D016753:Interleukin-10; C000606430:INPP5D protein, human; C000606433:Inpp5d protein, mouse; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
keywords: Commensal bacteria; Crohn’s disease; IL-10; MicroRNA-155; SHIP-1