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Am J Physiol Endocrinol Metab (May 21, 2002). doi:10.1152/ajpendo.00008.2002
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Articles in PresS, published online ahead of print May 21, 2002
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00008.2002
Submitted on January 9, 2002
Accepted on May 8, 2002

Enhancement of the inducible nitric oxide synthase activation by retinoic acid is mimmicked by RAR{alpha} agonist in vivo

Carole Seguin-Devaux1, Yvan Devaux1, Veronique Latger-Cannard2, Sandrine Grosjean3, Cecile Rochette-Egly4, Faiez Zannad1, Claude Meistelman5, Paul-Michel Mertes6, and Dan Longrois3*

1 UPRESS-EA 3447 Lesions-Reparation : Remodelage Cardiaque et Arteriel, Faculte de Medecine, Nancy, France
2 Hematologie Biologique, Centre Hospitalier et Universitaire Brabois, Nancy, France
3 UPRESS-EA 3447 Lesions-Reparation : Remodelage Cardiaque et Arteriel, Faculte de Medecine, Nancy, France; Anesthesie Reanimation Chirurgicale, Centre Hospitalier et Universitaire Brabois, Nancy, France
4 Institut de Genetique et de Biologie Moleculaire, Illkirch, France
5 Anesthesie Reanimation Chirurgicale, Centre Hospitalier et Universitaire Brabois, Nancy, France
6 UPRESS-EA 3447 Lesions-Reparation : Remodelage Cardiaque et Arteriel, Faculte de Medecine, Nancy, France; Anesthesie Reanimation Chirurgicale, Centre Hospitalier et Universitaire Hopital Central, Nancy, France

* To whom correspondence should be addressed. E-mail: d.longrois{at}chu-nancy.fr.

We have previously shown that all-trans retinoic acid (atRA), the active metabolite of vitamin A, enhances the activation of the inducible NO synthase (NOS2) pathway, a component of innate immunity, in rats in vivo. We investigated the relative contribution of retinoic acid receptor {alpha} (RAR{alpha}) and retinoid X receptors (RXRs) to NOS2 activation triggered by lipopolysaccharide (LPS). Five day supplementation with 10 mg/kg of either atRA or the RAR{alpha} selective agonist Ro 40-6055 but not with 10 mg/kg of the pan RXRs agonist Ro 25-7386 enhanced the LPS-induced NOS2 mRNA, protein expression in the liver and plasma nitrite/nitrate concentration. Both atRA and the RAR{alpha} agonist (but not the RXRs agonist) increased the number of peripheral T helper lymphocytes and plasma interferon-{gamma} concentration. Synergism between retinoids and LPS on NOS2 activation within an organ coincided with synergism on Interferon Regulatory Factor (IRF)-1 mRNA expression but not with the level of expression of the RAR{alpha} protein. These results suggest that, in vivo, atRA activates NOS2 through RAR{alpha} and contribute to characterize the complex effect of retinoids on the host inflammatory/immune response.






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