IL-1alpha and TNFalpha down-regulate CRH receptor-2 mRNA expression in the mouse heart.
Two receptors (CRH receptor type 1 and CRH receptor type 2) have been identified for the stress-induced neuropeptide, CRH and related peptides, urocortin, and urocortin II. We previously found marked down-regulation of cardiac CRH receptor type 2 expression following administration of bacterial endotoxin, lipopolysaccharide, a model of systemic immune activation, and inflammation. We postulated that inflammatory cytokines may regulate CRH receptor type 2. We show that systemic IL-1alpha administration significantly down-regulates CRH receptor type 2 mRNA in mouse heart. In addition, TNFalpha treatment also reduces CRH receptor type 2 mRNA expression, although the effect was not as marked as with IL-1alpha. However, CRH receptor type 2 mRNA expression is not altered in adult mouse ventricular cardiomyocytes stimulated in vitro with TNFalpha or IL-1alpha. Thus, cytokine regulation may be indirect. Exogenous administration of corticosterone in vivo or acute restraint stress also reduces cardiac CRH receptor type 2 mRNA expression, but like cytokines, in vitro corticosterone treatment does not modulate expression in cardiomyocytes. Interestingly, treatment with urocortin significantly decreases CRH receptor type 2 mRNA in cultured cardiomyocytes. We speculate that in vivo, inflammatory mediators such as lipopolysaccharide and/or cytokines may increase urocortin, which in turn down-regulates CRH receptor type 2 expression in the heart. Because CRH and urocortin increase cardiac contractility and coronary blood flow, impaired CRH receptor type 2 function during systemic inflammation may ultimately diminish the adaptive cardiac response to adverse conditions.[1]References
- IL-1alpha and TNFalpha down-regulate CRH receptor-2 mRNA expression in the mouse heart. Coste, S.C., Heldwein, K.A., Stevens, S.L., Tobar-Dupres, E., Stenzel-Poore, M.P. Endocrinology (2001) [Pubmed]
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