title: GPR120, a potential therapeutic target for experimental colitis in IL-10 deficient mice.
abstract: It has been proved that interleukin-10-knockout (IL-10 KO) mice display the most similar characteristics to that of human Crohn's disease (CD). Docosahexaenoic acid (DHA) has well established beneficial effects on human and animal models health with potent anti-inflammatory effects with poorly understood mechanisms. This study was aimed at figuring out whether DHA could ameliorate the Crohn's colitis by activating GPR120 and whether GPR120 could be a potential therapeutic target for CD.16 week-old mice included in our present study were divided into three groups, WT group, IL-10 KO group and DHA group(IL-10 KO mice with DHA treatment, i.g., 35.5mg/kg/d), containing 8 mice in each group. The severity of colitis, pro-inflammatory cytokines concentrations, the expression/distribution of protein GPR120 and TAK1/IKK-α/IkB-α/p65 pathway in the proximal colons were evaluated at the end of the experiment. Administration of DHA showed promising results in the experimental chronic colitis (demonstrated by reduced infiltration of inflammatory cells, lowered inflammation scores, decreased pro-inflammatory cytokines) and body weight loss improvement. Moreover, in the DHA-treated mice, enhanced expression and improved distribution integrity of protein GPR120 were observed, which was probably associated with the regulation of TAK1/IKK-α/IkB-α/p65 pathway. Our results indicated that triggering GPR120 via the inhibition of TAK1/IKK-α/IkB-α/p65 pathway might be an important target for Crohn's colitis.
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215000, Jiangsu, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of General Surgery, Taizhou People's Hospital, Medical School of Nantong University, Taizhou, 225300, Jiangsu, China.
authors.forename: Honggang
authors.initials: H
authors.lastname: Wang
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, 210000, Jiangsu, China.
authors.forename: Peiliang
authors.initials: P
authors.lastname: Shi
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215000, Jiangsu, China.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, 215000, Jiangsu, China.|Orthopedic Institute, Soochow University, Suzhou, 215000, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003092:Colitis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D020022:Genetic Predisposition to Disease; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000172:deficiency* / Q000235:genetics; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058990:Molecular Targeted Therapy; D010641:Phenotype; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015431:Weight Loss / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; C498007:FFAR4 protein, mouse; D005765:Gastrointestinal Agents; C556062:IL10 protein, mouse; D018836:Inflammation Mediators; D043562:Receptors, G-Protein-Coupled; D016753:Interleukin-10; D004281:Docosahexaenoic Acids
keywords: Crohn’s disease; GPR120; TAK1/IKK-α/IkB-α/p65 pathway; colitis; docosahexaenoic acid