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.
6-OAU是G蛋白偶联受体84（GPR84）的特异性激动剂[1]，可以诱导PMNs（polymorphonuclear leukocytes）和巨噬细胞的趋化以及巨噬细胞的促炎反应[2]。6-OAU通过上调Akt、ERK和核因子κB（NFκB）的信号通路，导致关键炎症细胞因子和趋化因子的表达增加，从而增强巨噬细胞的炎症反应[3]。6-OAU还具有抗菌能力，具有成为对抗布鲁氏菌病和其他细胞内病原体或炎症性疾病药物的潜力[2]。
6-OAU（0.01nM~0.1mM；2h）在Gqi5嵌合体存在的情况下，通过PI试验（phosphoinositide accumulation assay）测定在HEK293细胞中激活GPR84的EC50为105nM[1]；6-OAU（0~10μM；4h）可以增加LPS处理的人外周PMNs中IL-8的分泌[1]；6-OAU（0.001nM~10mM；30min）激活GPR84后使其与Gαi蛋白结合，从而抑制cAMP的产生，6-OAU在GPR84-CHO中抑制cAMP产生的EC50为14nM[3]；6-OAU（1μM；30、60、90、120和240min）可以促进LPS处理的BMDMs（bone marrow-derived macrophages）炎症因子和趋化因子的表达增强[3]；6-OAU（2μM；4h）可减少Brucella abortus和Salmonella在RAW264.7细胞上的粘附[2]。
6-OAU（10mg/kg；静脉注射）导致雌性Lewis大鼠血清中趋化因子CXCL1升高，引发炎症反应[1]；6-OAU（2μM, 100μL/只；1周；灌胃）可减少Brucella在肝脏和脾脏的增殖，增强对Brucella感染的抵抗力[2]。