Urocortin induces interleukin-6 release from rat cardiomyocytes through p38 MAP kinase, ERK and NF-κB activation

Man Huang, Duraisamy Kempuraj, Nikoletta Papadopoulou, Taxiarchis Kourelis, Jill Donelan, Akrivi Manola, Theoharis C. Theoharides

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

CRH and its structurally related peptide urocortin (Ucn) are released under stress. Ucn is a potent agonist for CRH-receptor 2 (CRH-R2), which is strongly expressed in rodent heart. Stress induces Ucn mRNA expression in the heart, where it may be cardioprotective. However, increasing evidence indicates that Ucn may also have pro-inflammatory actions. Here, we show that neonatal rat cardiomyocytes express CRH-R2 by western blot analysis and Ucn induces interleukin-6 (IL-6) release in a time- and dose-dependent fashion. Ucn stimulates activation of ERK and p38 MAP kinases, while both MEK1 and p38 inhibitor block Ucn-induced IL-6 release. Ucn also activates nuclear factor kappa B (NF-κB) and a NF-κB inhibitor blocks Ucn-induced IL-6 release. Finally, the CRH-R antagonists α-helical (9-41) CRH and astressin-2B completely inhibit Ucn-induced IL-6 release, as well as activation of ERK, p38, and NF-κB. These findings indicate that Ucn induces IL-6 synthesis and release from neonatal rat cardiomyocytes. Our findings suggest that even though Ucn may confirm some protection on cardiomyocyte survival, it can also release IL-6, which is an independent risk factor for acute coronary syndrome. The precise role of cardiac Ucn in vivo remains to be elucidated.

Original languageEnglish (US)
Pages (from-to)397-405
Number of pages9
JournalJournal of Molecular Endocrinology
Volume42
Issue number5
DOIs
StatePublished - Jul 1 2009

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ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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