6-OAU is a specific agonist of G protein-coupled receptor 84 (GPR84) [1] which can induce chemotaxis of polymorphonuclear leukocytes (PMNs) and macrophages as well as a pro-inflammatory response in macrophages [2]. 6-OAU enhances the inflammatory response in macrophages by upregulating the Akt, ERK, and the nuclear factor κB (NFκB) signaling pathways, which causes an increase in expression of key inflammatory cytokines and chemokines [3]. 6-OAU also has anti-bacterial ability and can be a potential candidate to against brucellosis and possibly other intracellular pathogens or inflammatory diseases [2].
6-OAU (0.01nM~0.1mM; 2h) activated human GPR84 in the presence of Gqi5 chimera in HEK293 cells with an EC50 of 105nM in the phosphoinositide accumulation assay (PI assay) [1]; 6-OAU (0~10μM; 4h) increased the secretion of IL-8 from LPS-stimulated human peripheral PMNs [1]; 6-OAU (0.001nM~10mM; 30min) activated GPR84 to bind to the Gαi protein, leaded to an inhibition of the production of cAMP with an EC50 of 14nM in CHO cells transfected with the human GPR84 receptor (GPR84-CHO) [3]; 6-OAU (1μM; 30, 60, 90, 120, and 240min) promoted enhanced expression of inflammatory cytokines and chemokines in LPS pre-treated Bone Marrow-Derived Macrophages (BMDMs) [3]; 6-OAU (2μM; 4h) reduced the number of Brucella abortus and Salmonella adhered to the RAW264.7 cells [2].
6-OAU (10mg/kg; i.v.) leaded to the elevation of chemokine CXCL1 in the serum, triggered an inflammatory response in female Lewis rats [1]; 6-OAU (2μM, 100μL/mouse; one week; i.g.) reduced the proliferation of Brucella in the liver and spleen and enhanced the resistance to Brucella infection [2].
References:
[1] Suzuki M, Takaishi S, Nagasaki M, et al. Medium-chain fatty acid-sensing receptor, GPR84, is a proinflammatory receptor [J]. Journal of Biological Chemistry, 2013, 288(15): 10684-10691.
[2] Reyes A W B, Kim H, Huy T X N, et al. Immune-metabolic receptor GPR84 surrogate and endogenous agonists, 6-OAU and lauric acid, alter Brucella abortus 544 infection in both in vitro and in vivo systems [J]. Microbial Pathogenesis, 2021, 158: 105079.
[3] Recio C, Lucy D, Purvis G S D, et al. Activation of the immune-metabolic receptor GPR84 enhances inflammation and phagocytosis in macrophages [J]. Frontiers in Immunology, 2018, 9: 1419.