GPR120, a potential therapeutic target for experimental colitis in IL-10 deficient mice.

Jie Zhao,Wenbo Wang,Peiliang Shi,Ye Sun,Honggang Wang

doi:10.18632/oncotarget.14210

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.

Highlights

Crohn disease (CD) is a chronic inflammatory bowel disease (IBD) involves the entire gastrointestinal tract with no certain etiology [1]
This study was aimed at figuring out whether Docosahexaenoic acid (DHA) could ameliorate the Crohn’s colitis by activating GPR120 and whether GPR120 could be a potential therapeutic target for Crohn’s disease (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
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

Summary

Introduction

Crohn disease (CD) is a chronic inflammatory bowel disease (IBD) involves the entire gastrointestinal tract with no certain etiology [1]. Omega-3 fatty acids (w-3 FAs), mainly docosahexaenoic acid (DHA) and ecosapentaenoic acid (EPA), have well established beneficial effects on human and animal models health with potent anti-inflammatory effects [6]. Nuclear receptor PPARγ and the G proteincoupled receptors (GPCRs) have been suggested to be the molecular targets for the anti-inflammatory effects of w-3 FAs reported by recent pharmacological studies [13, 14]. Studies have shown that GPR120 is a functional w-3 FA receptor/sensor and it can mediate potent anti-inflammatory effects in vivo by repressing macrophageinduced tissue inflammation [18]. 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 by mediating the inflammatory pathway

Objectives

Methods

Results

Conclusion