Regulatory potential of ethanol and retinoic acid on human monocyte functions.
Retinoic acid (RA), a metabolic product of vitamin A, has been shown to affect a variety of immune functions, including monocytes. Monocyte functions and mediator production are also modulated by ethanol exposure. This study demonstrates that therapeutic doses of RA (0.1-10 microM) significantly increase transforming growth factor-beta (TGF beta) production both in THP-1, human myelomonocytic cells, and in human peripheral blood monocytes. We have previously reported TGF beta induction by ethanol in human M theta. Combination of RA stimulation with acute in vitro ethanol treatment, however, resulted in significantly lower M theta TGF beta production than TGF beta levels induced by RA alone (p < 0.003). Down-regulation of M theta TGF beta production by ethanol was tested at the concentration range of 25-150 mM and occurred both at high and low RA concentrations (10-0.1 microM). In contrast to its inhibitory effect on RA-induced M theta TGF beta production, ethanol augmented TGF beta production induced by muramyl dipeptide (20 micrograms/ml), suggesting that ethanol can either up- or down-regulate M theta TGF beta production, depending on the costimulatory factors. RA also induced a moderate increase in M theta tumor necrosis factor-alpha (TNF alpha) production, which was down-regulated by ethanol both at the level of secreted and cell-associated TNF alpha. In addition to regulation of cytokine production, both RA and ethanol decreased expression of CD4 on THP-1 cells. The degree of inhibition of CD4 expression by RA was more significant than by ethanol, but RA-induced decrease in CD4 expression was not significantly affected by the combined stimulation with ethanol.(ABSTRACT TRUNCATED AT 250 WORDS)
Szabo
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G
Department of Surgery, University of Massachusetts Medical Center, Worcester 01655.
Puppolo
M
M
Verma
B
B
Catalano
D
D
D015704:CD4 Antigens / Q000378:metabolism*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015704:CD4 Antigens; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; D014212:Tretinoin