Retinoic acid inhibits interleukin-1-induced cytokine synthesis in human monocytes.
Retinoids are pluripotent morphogens whose effects on gene expression are mediated through specific intracellular receptors. They have certain anti-inflammatory effects in vivo, the basis of which is not clearly understood. To characterize mechanisms involved with potential anti-inflammatory actions of retinoids, we studied the effects of retinoic acid (RA) on cytokine production in human peripheral blood monocytes. RA differentially modulated the expression of interleukin-1 beta (IL-1 beta), IL-6, and IL-8 mRNAs depending on the inducing stimulus. While phorbol myristate acetate-induced IL-1 beta and IL-8 mRNA expression was increased by RA (IL-6 could not be induced by this pathway in monocytes), IL-1 beta-induced expression of IL-1 beta and IL-8 was markedly reduced and IL-6 gene expression was almost completely suppressed. Lipopolysaccharide (LPS)-induced cytokine synthesis was only slightly reduced and this required a longer preincubation (> 72 h) of monocytes with RA. IL-1-induced de novo synthesis of IL-6 protein and secretion of biologically active IL-6 were also inhibited by RA. The inhibition pattern of RA was different from that of dexamethasone, which inhibited both IL-1 and LPS effects. In summary, our data show that RA regulates monocyte cytokine expression selectively in response to the particular stimuli. Inhibition of IL-1 beta-induced cytokine expression provides a mechanism that can explain some of the anti-inflammatory effects of RA.
Gross
V
V
Sam and Rose Stein Institute for Research on Aging, University of California, San Diego, La Jolla 92093-0663.
Villiger
P M
PM
Zhang
B
B
Lotz
M
M
D001483:Base Sequence; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D014212:Tretinoin / Q000494:pharmacology*
D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D007378:Interleukins; D012333:RNA, Messenger; D014212:Tretinoin