RESUMEN
G protein-coupled receptor 84 (Gpr84) is reportedly activated by medium-chain fatty acids and is involved in the pathology of liver fibrosis. Inflammatory stimulants, such as lipopolysaccharide and tumor necrosis factor-α, upregulate Gpr84 expression. However, the detailed molecular mechanism by which Gpr84 is induced remains unknown. Inflammatory stimulation also evokes endoplasmic reticulum (ER) stress, but there has been no direct evidence to link Gpr84 expression and the ER stress response. Administration of tunicamycin (Tm) provokes ER stress and acute steatosis in the liver tissue of mice. Here, in situ hybridization analysis revealed that induction of Gpr84 expression occurred in parenchymal cells in the liver tissue following Tm administration. Gene expression analysis using a reporter assay showed that the intron 1 region of Gpr84 was involved in induction of the gene under ER stress conditions. Furthermore, Tm-dependent upregulation of Gpr84 was blocked by the small chemical compound AEBSF, an inhibitor of ER stress transducers, in vitro and in vivo. In conclusion, the current study marks the discovery that the ER stress agent Tm induces the expression of Gpr84.