PMID- 12169446 OWN - NLM STAT- MEDLINE DCOM- 20020923 LR - 20161124 IS - 0193-1849 (Print) IS - 0193-1849 (Linking) VI - 283 IP - 3 DP - 2002 Sep TI - Enhancement of the inducible NO synthase activation by retinoic acid is mimicked by RARalpha agonist in vivo. PG - E525-35 AB - We have previously shown that all-trans 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 receptor-alpha (RARalpha) and retinoid X receptors (RXRs) to NOS II activation triggered by LPS. Five-day supplementation with 10 mg/kg of either atRA or the RARalpha 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 RARalpha agonist (but not the RXR agonist) increased the number of peripheral T helper lymphocytes and plasma interferon-gamma 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 RARalpha protein. These results suggest that, in vivo, atRA activates NOS II through RARalpha and contributes to characterizing the complex effect of retinoids on the host inflammatory/immune response. FAU - Seguin-Devaux, Carole AU - Seguin-Devaux C AD - Unite Propre de Recherche et d'Enseignement Superieur-Equipe d'Accueil 3447 Lesions-Reparation: Remodelage Cardiaque et Arteriel, Faculte de Medecine, Universite Henri Poincare, Nancy I, France. FAU - Devaux, Yvan AU - Devaux Y FAU - Latger-Cannard, Veronique AU - Latger-Cannard V FAU - Grosjean, Sandrine AU - Grosjean S FAU - Rochette-Egly, Cecile AU - Rochette-Egly C FAU - Zannad, Faiez AU - Zannad F FAU - Meistelman, Claude AU - Meistelman C FAU - Mertes, Paul-Michel AU - Mertes PM FAU - Longrois, Dan AU - Longrois D LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Physiol Endocrinol Metab JT - American journal of physiology. Endocrinology and metabolism JID - 100901226 RN - 0 (Benzoates) RN - 0 (DNA-Binding Proteins) RN - 0 (Interferon Regulatory Factor-1) RN - 0 (Irf1 protein, rat) RN - 0 (Phosphoproteins) RN - 0 (RNA, Messenger) RN - 0 (Rara protein, rat) RN - 0 (Receptors, Retinoic Acid) RN - 0 (Retinoic Acid Receptor alpha) RN - 0 (Retinoid X Receptors) RN - 0 (Tetrahydronaphthalenes) RN - 0 (Transcription Factors) RN - 102121-60-8 (Am 580) RN - 5688UTC01R (Tretinoin) RN - 82115-62-6 (Interferon-gamma) RN - EC 1.14.13.39 (Nitric Oxide Synthase) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.13.39 (Nos2 protein, rat) SB - IM MH - Animals MH - Benzoates/*pharmacology MH - Blood Cell Count MH - DNA-Binding Proteins/genetics MH - Enzyme Activation/drug effects MH - Interferon Regulatory Factor-1 MH - Interferon-gamma/blood/genetics MH - Liver/drug effects/metabolism MH - Lung/drug effects/metabolism MH - Male MH - Nitric Oxide Synthase/genetics/*metabolism MH - Nitric Oxide Synthase Type II MH - Phosphoproteins/genetics MH - RNA, Messenger/metabolism MH - Rats MH - Rats, Inbred WKY MH - Receptors, Retinoic Acid/*agonists/metabolism MH - Retinoic Acid Receptor alpha MH - Retinoid X Receptors MH - Spleen/drug effects/metabolism MH - T-Lymphocyte Subsets/cytology/drug effects MH - Tetrahydronaphthalenes/*pharmacology MH - Transcription Factors/agonists MH - Tretinoin/*pharmacology EDAT- 2002/08/10 10:00 MHDA- 2002/09/24 06:00 CRDT- 2002/08/10 10:00 PHST- 2002/08/10 10:00 [pubmed] PHST- 2002/09/24 06:00 [medline] PHST- 2002/08/10 10:00 [entrez] AID - 10.1152/ajpendo.00008.2002 [doi] PST - ppublish SO - Am J Physiol Endocrinol Metab. 2002 Sep;283(3):E525-35. doi: 10.1152/ajpendo.00008.2002.