Enhancement of the inducible NO synthase activation by retinoic acid is mimicked by RARalpha agonist in vivo.
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.
Seguin-Devaux
Carole
C
Unité Propre de Recherche et d'Enseignement Supérieur-Equipe d'Accueil 3447 Lésions-Réparation: Remodelage Cardiaque et Artériel, Faculté de Médecine, Université Henri Poincaré, Nancy I, France.
Devaux
Yvan
Y
Latger-Cannard
Véronique
V
Grosjean
Sandrine
S
Rochette-Egly
Cécile
C
Zannad
Faiez
F
Meistelman
Claude
C
Mertes
Paul-Michel
PM
Longrois
Dan
D
D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D001772:Blood Cell Count; D004268:DNA-Binding Proteins / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D010750:Phosphoproteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D018168:Receptors, Retinoic Acid / Q000819:agonists* / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D014157:Transcription Factors / Q000819:agonists; D014212:Tretinoin / Q000494:pharmacology*
D001565:Benzoates; D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; C494259:Irf1 protein, rat; D010750:Phosphoproteins; D012333:RNA, Messenger; C000607073:Rara protein, rat; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D013764:Tetrahydronaphthalenes; D014157:Transcription Factors; C068073:Am 580; D014212:Tretinoin; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat