Enhancement of the inducible NO synthase activation by retinoic acid is mimicked by RAR␣ agonist in vivo. Am J Physiol Endocrinol Metab 283: E525-E535, 2002. First published May 21, 2002 10.1152/ ajpendo.00008.2002We have previously shown that alltrans retinoic acid (atRA), the active metabolite of vitamin A, enhances the activation of the inducible nitric oxide synthase (NOS II) pathway, a component of innate immunity, in rats in vivo. We investigated the relative contribution of retinoic acid

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... receptor-␣ (RAR␣) and retinoid X receptors (RXRs) to NOS II activation triggered by LPS. Five-day supplementation with 10 mg/kg of either atRA or the RAR␣ selective agonist Ro-40-6055, but not with 10 mg/kg of the pan-RXR agonist Ro-25-7386, enhanced the LPS-induced NOS II mRNA, protein expression in liver, and plasma nitrite/nitrate concentration. Both atRA and the RAR␣ agonist (but not the RXR agonist) increased the number of peripheral T helper lymphocytes and plasma interferon-␥ concentration. Synergism between retinoids and LPS on NOS II activation within an organ coincided with synergism on interferon regulatory factor-1 mRNA expression but not with the level of expression of the RAR␣ protein. These results suggest that, in vivo, atRA activates NOS II through RAR␣ and contributes to characterizing the complex effect of retinoids on the host inflammatory/immune response. synthetic retinoids; inducible nitric oxide synthase; T helper lymphocyte; interferon type II; interferon regulatory factor-1 VITAMIN A DEFICIENCY has been associated with increased incidence of infection, which gained its reputation as an "anti-infective" vitamin. Nevertheless, the beneficial anti-infective effects of vitamin A supplementation are controversial (11, 36, 42) . Vitamin A and its active metabolite all-trans retinoic acid (atRA) modulate host