Zhao Yan-Yan, Fu Hui, Liang Xiang-Yan, Zhang Bi-Lin, Wei Lan-Lan, Zhu Juan-Xia, Chen Ming-Wei, Zhao Yu-Feng
Institute of Basic Medical Sciences, Xi'an Medical University, Xi'an, 710021, China.
Shaanxi Provincial Research Center for Prevention and Treatment of Respiratory Diseases, Xi'an Medical University, Xi'an, 710021, China.
Cell Biol Int. 2020 Jan;44(1):89-97. doi: 10.1002/cbin.11204. Epub 2019 Jul 31.
Free fatty acid receptor G protein-coupled receptor 120 (GPR120) is highly expressed in macrophages and was reported to inhibit lipopolysaccharide (LPS)-stimulated cytokine expression. Under inflammation, macrophages exhibit striking functional changes, but changes in GPR120 expression and signaling are not known. In this study, the effects of LPS treatment on macrophage GPR120 expression and activation were investigated. The results showed that LPS inhibited GPR120 expression in mouse macrophage cell line Ana-1 cells. Moreover, LPS treatment inhibited GPR120 expression in mouse alveolar macrophages both in vitro and in vivo. The inhibitory effect of LPS on GPR120 expression was blocked by Toll-like receptor 4 (TLR4) inhibitor TAK242 and p38 mitogen-activated protein kinase inhibitor LY222820, but not by ERK1/2 inhibitor U0126 and c-Jun N-terminal kinase inhibitor SP600125. LPS-induced inhibition of GPR120 expression was not attenuated by GPR120 agonists TUG891 and GW9508. TUG891 inhibited the phagocytosis of alveolar macrophages, and LPS treatment counteracted the effects of TUG891 on phagocytosis. These results indicate that pretreatment with LPS inhibits GPR120 expression and activation in macrophages. It is suggested that LPS-induced inhibition of GPR120 expression is a reaction enhancing the LPS-induced pro-inflammatory response of macrophages.
游离脂肪酸受体G蛋白偶联受体120（GPR120）在巨噬细胞中高表达，据报道可抑制脂多糖（LPS）刺激的细胞因子表达。在炎症状态下，巨噬细胞表现出显著的功能变化，但GPR120表达和信号传导的变化尚不清楚。在本研究中，研究了LPS处理对巨噬细胞GPR120表达和激活的影响。结果表明，LPS抑制小鼠巨噬细胞系Ana-1细胞中GPR120的表达。此外，LPS处理在体外和体内均抑制小鼠肺泡巨噬细胞中GPR120的表达。LPS对GPR120表达的抑制作用被Toll样受体4（TLR4）抑制剂TAK242和p38丝裂原活化蛋白激酶抑制剂LY222820阻断，但未被ERK1/2抑制剂U0126和c-Jun氨基末端激酶抑制剂SP600125阻断。GPR120激动剂TUG891和GW9508未减弱LPS诱导的GPR120表达抑制。TUG891抑制肺泡巨噬细胞的吞噬作用，LPS处理抵消了TUG891对吞噬作用的影响。这些结果表明，LPS预处理可抑制巨噬细胞中GPR120的表达和激活。提示LPS诱导的GPR120表达抑制是一种增强LPS诱导的巨噬细胞促炎反应的反应。
