A commentary on the inhibition by retinoids of leukotriene B4 production in leukocytes.
The order of potency of retinoids as inhibitors of A23187-induced production of leukotriene B4 (LTB4) in human polymorphonuclear leukocytes (PMN) was retinoic acid greater than retinal greater than retinol. However, the conversion of exogenous arachidonate (AA) to LTB4 by PMN homogenates was inhibited in the rank order retinol greater than retinal much greater than retinoic acid. The agreement between active concentrations of retinol in these two systems is consistent with this compound acting directly to inhibit AA metabolism: this is not so for the other retinoids. The order of potency for inhibition of phorbol dibutyrate (PDBu)-stimulated superoxide (O-2) production in HL60 granulocytes was retinol greater than retinoic acid much greater than retinal (inactive); neither retinol nor retinal displaced [3H]PDBu from HL60 cells. We conclude that inhibition of LTB4 production by retinoic acid and retinal is neither through inhibition of AA metabolism nor through inhibition of protein kinase C.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002460:Cell Line; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D007975:Leukotriene B4 / Q000096:biosynthesis*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D012172:Retinaldehyde / Q000494:pharmacology; D012176:Retinoids / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D014801:Vitamin A / Q000494:pharmacology
D001095:Arachidonic Acids; D010703:Phorbol Esters; D012176:Retinoids; D013481:Superoxides; D014801:Vitamin A; D007975:Leukotriene B4; D016718:Arachidonic Acid; D015240:Phorbol 12,13-Dibutyrate; D014212:Tretinoin; D011493:Protein Kinase C; D012172:Retinaldehyde