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: Yi Li, Yun Tian, Weiming Zhu, Jianfeng Gong, Zhen Guo, Feilong Guo, Lili Gu, Jieshou Li
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 116 Pg. 100-6 (09 15 2016) ISSN: 1873-2968 [Electronic] England
• PMID: 27395764 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• IL10 protein, human
• IL10 protein, mouse
• MIRN155 microRNA, human
• MicroRNAs
• Mirn155 microRNA, mouse
• Interleukin-10
• INPP5D protein, human
• Inpp5d protein, mouse
• Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases

Topics

• Animals
• Colitis (etiology, immunology, metabolism, therapy)
• Colon (immunology, metabolism, microbiology)
• Crohn Disease (immunology, metabolism, microbiology)
• Dysbiosis (microbiology, physiopathology)
• Female
• Germ-Free Life
• Humans
• Interleukin-10 (genetics, metabolism)
• Intestinal Mucosa (immunology, metabolism, microbiology)
• Male
• Mice, Inbred C57BL
• Mice, Knockout
• MicroRNAs (antagonists & inhibitors, metabolism)
• Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases (genetics, metabolism)
• RNA Interference
• Signal Transduction
• Specific Pathogen-Free Organisms
• Up-Regulation