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Immunité innée et coeur : expression et régulation de deux effecteurs, la NO synthase inductible et le complément C3

Abstract : An intense inflammatory response involving innate immunity effectors is observed during sepsis and after ischemia-reperfusion. An uncontrolled inflammatory response is detrimental for the host in situations such as septic shock. The aims of this study were to document the expression and regulation of two effectors of innate immunity, inducible nitric oxide synthase (NOS2) and component C3 of the complement cascade. The main results of our study are (i) cardiac myocytes express NOS2 during the development of post-ischemic heart failure ; (ii) all-trans retinoic acid (atRA), the active metabolite of vitamin A, downregulates NOS2 expression in cardiac myocytes and cardiac micro-endothelial cells stimulated with lipopolysaccharide (LPS) or interleukin-1[bêta] (IL-1[bêta]) and interferon-[gamma] (IFN[gamma]). The mechanisms through which atRA decreases NOS2 expression are dependent upon the stimulus used. Indeed, a reduction in NOS2 abundance is observed when the pro-inflammatory stimulus is IL-1[bêta]/IFN[gamma] whereas a decrease in NOS2 mRNA half-life was observed when LPS/IFN[gamma] were used ; (iii) in an in vivo septic shock model in the rat, atRA supplementation increased the mortality rate along with NOS2 expression in several organs but not the heart ; (iv) neonatal rat cardiac myocytes express C3 protein after hypoxia/reoxygenation, and also after a pro-inflammatory stimulus using LPS. Myocardial infarction size following ischemia-reperfusion is significantly reduced in knockout mice for C3 or for complement receptors CD21 and CD35 (Cr2 KO mice). ln summary, rodent cardiac myocytes express NOS2 and C3, which are two main effectors of innate immunity. These results are an incentive to modulate these effectors during sepsis or after ischemia-reperfusion.
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Submitted on : Thursday, March 29, 2018 - 10:49:50 AM
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Sandrine Grosjean. Immunité innée et coeur : expression et régulation de deux effecteurs, la NO synthase inductible et le complément C3. Biologie moléculaire. Université Henri Poincaré - Nancy 1, 2002. Français. ⟨NNT : 2002NAN10298⟩. ⟨tel-01747034⟩



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