Zhao Jie, Wang Honggang, Shi Peiliang, Wang Wenbo, Sun Ye
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215000, Jiangsu, China.
Department of General Surgery, Taizhou People's Hospital, Medical School of Nantong University, Taizhou, 225300, Jiangsu, China.
Oncotarget. 2017 Jan 31;8(5):8397-8405. doi: 10.18632/oncotarget.14210.
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.
已证明白细胞介素-10基因敲除（IL-10 KO）小鼠表现出与人类克罗恩病（CD）最相似的特征。二十二碳六烯酸（DHA）对人和动物模型的健康具有明确的有益作用，具有强大的抗炎作用，但其机制尚不清楚。本研究旨在弄清楚DHA是否可以通过激活GPR120来改善克罗恩结肠炎，以及GPR120是否可能是CD的潜在治疗靶点。纳入我们本研究的16周龄小鼠分为三组，野生型（WT）组、IL-10 KO组和DHA组（用DHA治疗的IL-10 KO小鼠，灌胃，35.5mg/kg/d），每组8只小鼠。在实验结束时评估结肠炎的严重程度、促炎细胞因子浓度、近端结肠中蛋白GPR120的表达/分布以及TAK1/IKK-α/IκB-α/p65信号通路。给予DHA在实验性慢性结肠炎中显示出有前景的结果（表现为炎症细胞浸润减少、炎症评分降低、促炎细胞因子减少）以及体重减轻改善。此外，在DHA处理的小鼠中，观察到蛋白GPR120的表达增强和分布完整性改善，这可能与TAK1/IKK-α/IκB-α/p65信号通路的调节有关。我们的结果表明，通过抑制TAK1/IKK-α/IκB-α/p65信号通路触发GPR120可能是克罗恩结肠炎的一个重要靶点。
