IL-1α and TNFα down-regulate CHR receptor-2 mRNA expression in the mouse heart

Sarah C. Coste, Kurt A. Heldwein, Susan L. Stevens, Eric Tobar-Dupres, Mary Stenzel-Poore

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Abstract

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-1α administration significantly down-regulates CRH receptor type 2 mRNA in mouse heart. In addition, TNFα treatment also reduces CRH receptor type 2 mRNA expression, although the effect was not as marked as with IL-1α. However, CRH receptor type 2 mRNA expression is not altered in adult mouse ventricular cardiomyocytes stimulated in vitro with TNFα or IL-1α. 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.

Original languageEnglish (US)
Pages (from-to)3537-3545
Number of pages9
JournalEndocrinology
Volume142
Issue number8
DOIs
StatePublished - Jan 1 2001

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Corticotropin-Releasing Hormone Receptors
Interleukin-1
Down-Regulation
Urocortins
Messenger RNA
Cardiac Myocytes
Cytokines
Corticosterone
Lipopolysaccharides
Inflammation
Neuropeptides
Endotoxins

ASJC Scopus subject areas

  • Endocrinology

Cite this

IL-1α and TNFα down-regulate CHR receptor-2 mRNA expression in the mouse heart. / Coste, Sarah C.; Heldwein, Kurt A.; Stevens, Susan L.; Tobar-Dupres, Eric; Stenzel-Poore, Mary.

In: Endocrinology, Vol. 142, No. 8, 01.01.2001, p. 3537-3545.

Research output: Contribution to journalArticle

Coste, Sarah C. ; Heldwein, Kurt A. ; Stevens, Susan L. ; Tobar-Dupres, Eric ; Stenzel-Poore, Mary. / IL-1α and TNFα down-regulate CHR receptor-2 mRNA expression in the mouse heart. In: Endocrinology. 2001 ; Vol. 142, No. 8. pp. 3537-3545.
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