title: Accelerated degradation of retinoic acid by activated microglia.
abstract: In the brain, retinoic acid (RA) concentrations are under tight spatio-temporal control. Here, we show that challenge of primary mouse microglia with lipopolysaccharide (LPS) results in increased release of nitric oxide (NO) and tumor necrosis factor-α (TNF-α). Co-administration of RA attenuated microglial activation. Similarly, pretreatment with RA-metabolism inhibitor liarozole potently reduced NO and TNF-α release. Conversely, activated microglia showed increased protein expression of RA-degrading cytochromes CYP26A1, CYP26B1, CYP3A4 and CYP2C. Correspondingly, RA catabolism by activated microglia was significantly increased. Our results indicate that RA reduces microglial activation, but also, conversely, that the activation state of microglia influences RA metabolism.
authors: Center for Stroke Research Berlin, Charité Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany.
authors: Julian
authors: J
authors: Hellmann-Regen
authors: Golo
authors: G
authors: Kronenberg
authors: Ria
authors: R
authors: Uhlemann
authors: Dorette
authors: D
authors: Freyer
authors: Matthias
authors: M
authors: Endres
authors: Karen
authors: K
authors: Gertz
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D007093:Imidazoles / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D047488:Retinoid X Receptors / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014212:Tretinoin / Q000378:metabolism* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; C061121:liarozole