Effect of all-trans-retinoic acid on cytokine production in a murine macrophage cell line

All-trans-retinoic acid (RA) is a cancer chemopreventive agent and a plurip otent morphogen. It belongs to the class of retinoids that, besides being i nducers of differentiation and growth-inhibitos, exert immunomodulatory and anti-inflammatory functions by mechanisms that are not clearly understood. Macrophages play different roles in diverse physiological processes, inclu ding ones in orchestrating immune and inflammatory responses. Products of a ctivated macrophages such as interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), interleukin-6 interleukin-8, and nitric oxide (N O) are important regulators of inflammatory reactions. In this study J774A. 1 cells, a murine macrophage cell line, was used to study the effects of RA on the production of NO, TNF alpha and IL-1 beta. Cells were stimulated wi th lipopolysaccharide (LPS) with or without RA. RA depressed the levels of NO in a dose-dependent manner. NO production and subsequent nitrite accumul ation in the media peaked at 24 h, plateaued at 48 h, and remained at the s ame level through 72 h. The presence of RA decreased TNF alpha levels, meas ured by both bioassay and enzyme-linked immunosorbent assay (ELISA), but th ese did not correlate with increased mRNA expression measured by reverse-tr anscriptase polymerase chain reaction at 6 h after LPS stimulation. IL-1 be ta protein production measured by both ELISA and bioassay decreased with RA treatment. IL-1 beta mRNA expression was not affected by RA except at low doses. This study indicated that RA modulates cytokine production in J774A. 1 macrophage cells. Inhibition of inflammatory cytokine production may play a role in the anti-inflammatory activity of RA. The results suggested that effects of RA are complex and are rime and concentration dependent. (C) 20 00 International Society for Immunopharmacology. Published by Elsevier Scie nce Ltd. All rights reserved.