HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: JME-08-0120v1 42/5/397    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Huang, M. Articles by Theoharides, T. C Search for Related Content PubMed PubMed Citation Articles by Huang, M. Articles by Theoharides, T. C

¹ Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Pharmacology and Experimental Therapeutics² Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, CB# 7178, Thurston Bowles Building, Chapel Hill, North Carolina 27599-7178, USA³ Medical Faculty, Institute of Medical Microbiology, Immunology, and Hygiene, University of Cologne, Goldenfelsstraße 19-21, D-50935 Köln, Germany⁴ Millennium Pharmaceuticals, 40 Landsdowne Street, Cambridge, Massachusetts 02139, USA⁵ Departments of Internal Medicine⁶ Biochemistry, Tufts University School of Medicine, Tufts Medical Center, 136 Harrison Avenue, Boston, Massachusetts 02111, USA

(Correspondence should be addressed to T C Theoharides; Email: theoharis.theoharides{at}tufts.edu)

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-B) and a NF-B inhibitor blocks Ucn-induced IL-6 release. Finally, the CRH-R antagonists -helical (9–41) CRH and astressin-2B completely inhibit Ucn-induced IL-6 release, as well as activation of ERK, p38, and NF-B. 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.