AUTHOR=Wu Mengjiao , Li Qingfei , Mai Kangsen , Ai Qinghui 

TITLE=Regulation of Free Fatty Acid Receptor 4 on Inflammatory Gene Induced by LPS in Large Yellow Croaker (Larimichthys crocea)

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.703914

DOI=10.3389/fimmu.2021.703914

ISSN=1664-3224

ABSTRACT=<p>Free fatty acid receptor 4 (FFAR4) plays a key role in regulating the inflammatory response in mammals. The present study aimed to investigate the function of large yellow croaker FFAR4 on inflammation. In the present study, <italic>ffar4</italic> was widely expressed in 10 tissues of large yellow croaker including gill, head kidney and spleen. Further studies showed that treatment of head kidney macrophages with agonists (TUG891 or GSK137647A) or overexpression of <italic>ffar4</italic> reduced the mRNA expression of pro-inflammatory genes induced by LPS, and increased the expression of <italic>pparγ</italic>. Treatment of macrophages with antagonist AH7614 increased the mRNA expression of pro-inflammatory genes induced by LPS, and decreased the mRNA expression of <italic>pparγ</italic>. In order to verify the immunomodulatory effect of PPARγ, PPARγ was overexpressed in macrophages which significantly reduced the mRNA expression of pro-inflammatory genes <italic>il6</italic>, <italic>il1β</italic>, <italic>il8</italic>, <italic>tnfα</italic> and <italic>cox2</italic>. Moreover, results of dual-luciferase assays showed that PPARγ downregulated the transcriptional activity of <italic>il6</italic> and <italic>il1β</italic> promoters. In conclusion, FFAR4 showed anti-inflammatory effects on LPS-induced inflammation in large yellow croaker.</p>