title: RXR-induced TNF-alpha suppression is reversed by morphine in activated U937 cells.
abstract: Deficiency in vitamin A has been associated with adverse clinical outcomes in drug users with HIV-1 infection. Retinoids have been demonstrated to suppress proinflammatory cytokine production by immune cells in vitro. These effects are induced by ligand-mediated activation of the retinoid receptors--retinoic acid receptor (RAR) and retinoid X receptor (RXR). In these studies, the effects of all-trans-retinoid acid (ATRA, a RAR agonist), 9-cis-retinoic acid (9cis RA; RAR and RXR agonist), LG101305 (RXR agonist), LG100815 (RAR antagonist) and LG101208 (RXR antagonist) on TNF-alpha production by phytohemagglutanin-activated U937 cells and the modulation of these effects by morphine were examined. TNF-alpha production was suppressed in all cultures exposed to retinoid agonist and antagonist agents. For cells exposed to RXR agonists or RAR antagonist, incubation with morphine resulted in the reversal of TNF-alpha suppression and this effect was inhibited by naloxone. These data suggest that interactions between RXR and morphine are involved in the immune effects of retinoids on TNF-alpha production by activated U937 cells. Such information may be important for understanding interactions between drugs of abuse and immune function in individuals with chronic proinflammatory states such as HIV-1 infection.
authors.affiliation: Morehouse School of Medicine, Neuroscience Institute, 720 Westview Dr., S.W., Atlanta, GA 30310-1495, USA.
authors.forename: Liping
authors.initials: L
authors.lastname: Mou
authors.forename: Pamela
authors.initials: P
authors.lastname: Lankford-Turner
authors.forename: Michelle V
authors.initials: MV
authors.lastname: Leander
authors.forename: Reid P
authors.initials: RP
authors.lastname: Bissonnette
authors.forename: Robert M
authors.initials: RM
authors.lastname: Donahoe
authors.forename: Walter
authors.initials: W
authors.lastname: Royal
mesh_terms: D000077556:Alitretinoin; D000970:Antineoplastic Agents / Q000494:pharmacology; D003864:Depression, Chemical; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D018168:Receptors, Retinoic Acid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000276:immunology*; D047488:Retinoid X Receptors; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D013997:Time Factors; D014157:Transcription Factors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000276:immunology*; D014212:Tretinoin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D020298:U937 Cells / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; C424882:LG101305; D009292:Narcotic Antagonists; D009294:Narcotics; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D013764:Tetrahydronaphthalenes; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000077556:Alitretinoin; D009270:Naloxone; D014212:Tretinoin; D009020:Morphine