RGD Reference Report - Urocortin induces interleukin-6 release from rat cardiomyocytes through p38 MAP kinase, ERK and NF-kappaB activation. - Rat Genome Database

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

Authors: Huang, M  Kempuraj, D  Papadopoulou, N  Kourelis, T  Donelan, J  Manola, A  Theoharides, TC 
Citation: Huang M, etal., J Mol Endocrinol. 2009 May;42(5):397-405. Epub 2009 Feb 11.
RGD ID: 5130956
Pubmed: PMID:19211730   (View Abstract at PubMed)
DOI: DOI:10.1677/JME-08-0120   (Journal Full-text)

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




Biological Process

  

RGD Manual Annotations


  
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Species
Term
Qualifier
Evidence
With
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Original Reference(s)
Crhr2Mousep38 MAPK signaling pathway   ISOCrhr2 (Rattus norvegicus) RGD 

Genes (Rattus norvegicus)
Crhr2  (corticotropin releasing hormone receptor 2)

Genes (Mus musculus)
Crhr2  (corticotropin releasing hormone receptor 2)

Gene CRHR2 corticotropin releasing hormone receptor 2 Homo sapiens