RGD Reference Report - A new regulation of IL-6 production in adult cardiomyocytes by beta-adrenergic and IL-1 beta receptors and induction of cellular hypertrophy by IL-6 trans-signalling. - Rat Genome Database

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A new regulation of IL-6 production in adult cardiomyocytes by beta-adrenergic and IL-1 beta receptors and induction of cellular hypertrophy by IL-6 trans-signalling.

Authors: Szabo-Fresnais, N  Lefebvre, F  Germain, A  Fischmeister, R  Pomerance, M 
Citation: Szabo-Fresnais N, etal., Cell Signal. 2010 Jul;22(7):1143-52. Epub 2010 Mar 11.
RGD ID: 5128677
Pubmed: PMID:20227492   (View Abstract at PubMed)
DOI: DOI:10.1016/j.cellsig.2010.03.009   (Journal Full-text)

The sympathetic nervous system and pro-inflammatory cytokines play key roles in numerous cardiovascular disorders. Chronic beta-adrenergic receptor (beta-AR) stimulation in myocardium induces expression of pro-inflammatory cytokines, such as interleukin-1 (IL-1) and interleukin-6 (IL-6), which contribute to cardiac hypertrophy and failure. To evaluate the relationship between beta-AR stimulation and pro-inflammatory cytokines, we studied the effects of the beta-AR agonist isoprenaline (ISO) on IL-1-induced IL-6 production in adult rat ventricular myocytes (ARVMs). We report that ISO and IL-1 synergistically enhanced IL-6 gene expression and secretion. The synergistic effect of ISO was mimicked by cAMP elevating agents and involved the G(s) protein/cAMP/PKA signalling pathway, but not the exchange factor EPAC. To evaluate the contribution of IL-6 to cellular hypertrophy, we examined the signalling pathways stimulated by the membrane-bound IL-6 receptor (IL-6R), and the IL-6 soluble receptor (sIL-6R) involved in the mechanism named IL-6 trans-signalling. The IL-6/sIL-6R complex promoted a rapid and persistent phosphorylation of STAT3(Tyr705) in ARVMs. Moreover, IL-6 trans-signalling increased protein synthesis, c-fos gene expression and B-type natriuretic peptide secretion, three markers of cardiac hypertrophy. IL-6 trans-signalling also increased cell size. In contrast, IL-6 alone had no significant effect on either cell size or STAT3 phosphorylation although it induced phosphorylation of ERK1/2, AKT and S6K, demonstrating the presence of a functional IL-6R in ARVMs. Taken together, these results demonstrate that beta-AR stimulation synergises with IL-1 for IL-6 secretion in adult ventricular myocytes and indicate that IL-6 induces cardiac hypertrophy only via IL-6 trans-signalling. The IL-6 soluble receptor may thus serve as a switch for IL-6 to activate STAT3 phosphorylation and hypertrophy.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Il6Ratpositive regulation of ERK1 and ERK2 cascade  IDA  RGD 
Il6Ratpositive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il6  (interleukin 6)

Objects referenced in this article
Gene Il6r interleukin 6 receptor Rattus norvegicus

Additional Information