IL-10/microRNA-155/SHIP-1 signaling pathway is crucial for commensal bacteria induced spontaneous colitis

详细信息    查看全文

• 作者：Yi Li^a ; ¹ ; Yun Tian^b ; ¹ ; Weiming Zhu^a ; ^{juwiming@nju.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Jianfeng Gong^a ; Zhen Guo^a ; Feilong Guo^a ; Lili Gu^a ; Jieshou Li^a
• 关键词：CD ; Crohn&rsquo ; s disease ; GF ; germ-free ; IBD ; inflammatory bowel disease ; IL-10 ; interleukin-10 ; IL-10&minus ; /&minus ; IL-10 deficient ; miR-155 ; microRNA-155 ; SD ; standard deviation ; SPF ; specific pathogen-free ; SHIP-1 ; Src homology 2 domain-containing inositol 5-phosphatase 1 ; Tregs ; regulatory T cells ; UC ; ulcerative colitis
• 刊名：Biochemical Pharmacology
• 出版年：2016
• 出版时间：15 September 2016
• 年：2016
• 卷：116
• 期：Complete
• 页码：100-106
• 全文大小：1307 K

文摘

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.