Formyl peptide receptor 2 is an emerging modulator of inflammation in the liver

Formyl peptide receptors (FPRs), which are seven-membrane G-protein coupled receptors, recognize chemotactic signals to protect hosts from pathogenic infections and mediate inflammatory responses in the body. There are three isoforms of FPRs in humans-FPR1, FPR2, and FPR3-and they bind to N-formyl peptides, except FPR3, and to various endogenous agonists. Among FPR family members, FPR2 has a lower affinity for N-formyl peptides than FPR1 and binds with a wide range of endogenous or exogenous agonists. Thus, FPR2 is considered the most ambiguous member. Accumulating evidence has shown that FPR2 is involved in the host's defense against bacterial infection and inflammation in liver diseases, such as nonalcoholic fatty liver disease, liver fibrosis, and liver cancer, suggesting the pathophysiological relevance of FPR2 to the liver. However, FPR2 has been shown to promote or suppress inflammation, depending on the type of FPR2-expressing cell and FPR2-bound ligands in the liver. Therefore, it is important to understand FPR2's function per se and to elucidate the mechanism underlying immunomodulation initiated by ligand-activated FPR2 before suggesting FPR2 as a novel therapeutic agent for liver diseases. In this review, up-to-date knowledge of FPR2, with general information on the FPR family, is provided. We shed light on the dual action of FPR2 in the liver and discuss the hepatoprotective roles of FPR2 itself and FPR2 agonists in mediating anti-inflammatory responses.