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.
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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)
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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
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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
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