RGD Reference Report - IL-33 and ST2 comprise a critical biomechanically induced and cardioprotective signaling system. - Rat Genome Database

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IL-33 and ST2 comprise a critical biomechanically induced and cardioprotective signaling system.

Authors: Sanada, Shoji  Hakuno, Daihiko  Higgins, Luke J  Schreiter, Eric R  McKenzie, Andrew N J  Lee, Richard T 
Citation: Sanada S, etal., J Clin Invest. 2007 Jun;117(6):1538-49. doi: 10.1172/JCI30634. Epub 2007 May 10.
RGD ID: 40813740
Pubmed: PMID:17492053   (View Abstract at PubMed)
PMCID: PMC1865027   (View Article at PubMed Central)
DOI: DOI:10.1172/JCI30634   (Journal Full-text)

ST2 is an IL-1 receptor family member with transmembrane (ST2L) and soluble (sST2) isoforms. sST2 is a mechanically induced cardiomyocyte protein, and serum sST2 levels predict outcome in patients with acute myocardial infarction or chronic heart failure. Recently, IL-33 was identified as a functional ligand of ST2L, allowing exploration of the role of ST2 in myocardium. We found that IL-33 was a biomechanically induced protein predominantly synthesized by cardiac fibroblasts. IL-33 markedly antagonized angiotensin II- and phenylephrine-induced cardiomyocyte hypertrophy. Although IL-33 activated NF-kappaB, it inhibited angiotensin II- and phenylephrine-induced phosphorylation of inhibitor of NF-kappa B alpha (I kappa B alpha) and NF-kappaB nuclear binding activity. sST2 blocked antihypertrophic effects of IL-33, indicating that sST2 functions in myocardium as a soluble decoy receptor. Following pressure overload by transverse aortic constriction (TAC), ST2(-/-) mice had more left ventricular hypertrophy, more chamber dilation, reduced fractional shortening, more fibrosis, and impaired survival compared with WT littermates. Furthermore, recombinant IL-33 treatment reduced hypertrophy and fibrosis and improved survival after TAC in WT mice, but not in ST2(-/-) littermates. Thus, IL-33/ST2 signaling is a mechanically activated, cardioprotective fibroblast-cardiomyocyte paracrine system, which we believe to be novel. IL-33 may have therapeutic potential for beneficially regulating the myocardial response to overload.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IL1RL1HumanCardiomegaly severityISOIl1rl1 (Mus musculus) RGD 
IL33HumanCardiomegaly treatmentISOIl33 (Rattus norvegicus) RGD 
IL33HumanCardiomegaly  ISOIl33 (Mus musculus)protein:increased expression:cardiomyocyteRGD 
Il1rl1RatCardiomegaly severityISOIl1rl1 (Mus musculus) RGD 
Il1rl1MouseCardiomegaly severityIMP  RGD 
Il33RatCardiomegaly treatmentIDA  RGD 
Il33RatCardiomegaly  ISOIl33 (Mus musculus)protein:increased expression:cardiomyocyteRGD 
Il33MouseCardiomegaly treatmentISOIl33 (Rattus norvegicus) RGD 
Il33MouseCardiomegaly  IEP protein:increased expression:cardiomyocyteRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Il1rl1Ratcellular response to mechanical stimulus  IEP  RGD 
Il33Ratcellular response to mechanical stimulus  IEP  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Il33Ratprotein binding  IPIIl33 (Mus musculus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il1rl1  (interleukin 1 receptor-like 1)
Il33  (interleukin 33)

Genes (Mus musculus)
Il1rl1  (interleukin 1 receptor-like 1)
Il33  (interleukin 33)

Genes (Homo sapiens)
IL1RL1  (interleukin 1 receptor like 1)
IL33  (interleukin 33)


Additional Information