| http://purl.uniprot.org/citations/15574430 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15574430 | http://www.w3.org/2000/01/rdf-schema#comment | "In patients with congestive heart failure, high serum levels of the proinflammatory cytokine interleukin (IL)-18 were reported. A positive correlation was described between serum IL-18 levels and the disease severity. IL-18 has also been shown to induce atrial natriuretic factor (ANF) gene expression in adult cardiomyocytes. Because re-expression of the fetal gene ANF is mostly associated with hypertrophy, a hallmark of heart failure, we hypothesized that IL-18 induces cardiomyocyte hypertrophy. Treatment of the cardiomyocyte cell line HL-1 with IL-18 induced hypertrophy as characterized by increases in protein synthesis, phosphorylated p70 S6 kinase, and ribosomal S6 protein levels as well as cell surface area. Furthermore, IL-18 induced ANF gene transcription in a time-dependent manner as evidenced by increased ANF secretion and ANF promoter-driven reporter gene activity. Investigation into possible signal transduction pathways mediating IL-18 effects revealed that IL-18 activates phosphoinositide 3-kinase (PI3K), an effect that was blocked by wortmannin and LY-294002. IL-18 induced Akt phosphorylation and stimulated its activity, effects that were abolished by Akt inhibitor or knockdown. IL-18 stimulated GATA4 DNA binding activity and increased transcription of a reporter gene driven by multimerized GATA4-binding DNA elements. Pharmacological inhibition or knockdown studies revealed that IL-18 induced cardiomyocyte hypertrophy and ANF gene transcription via PI3K, PDK1, Akt, and GATA4. Most importantly, IL-18 induced ANF gene transcription and hypertrophy of neonatal rat ventricular myocytes via PI3K-, Akt-, and GATA4-dependent signaling. Together these data provide the first evidence that IL-18 induces cardiomyocyte hypertrophy via PI3K-dependent signaling, defines a mechanism of IL-18-mediated ANF gene transcription, and further supports a role for IL-18 in inflammatory heart diseases including heart failure."xsd:string |
| http://purl.uniprot.org/citations/15574430 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m411787200"xsd:string |
| http://purl.uniprot.org/citations/15574430 | http://purl.uniprot.org/core/author | "Nemer M."xsd:string |
| http://purl.uniprot.org/citations/15574430 | http://purl.uniprot.org/core/author | "Claycomb W.C."xsd:string |
| http://purl.uniprot.org/citations/15574430 | http://purl.uniprot.org/core/author | "Chandrasekar B."xsd:string |
| http://purl.uniprot.org/citations/15574430 | http://purl.uniprot.org/core/author | "Mummidi S."xsd:string |
| http://purl.uniprot.org/citations/15574430 | http://purl.uniprot.org/core/author | "Mestril R."xsd:string |
| http://purl.uniprot.org/citations/15574430 | http://purl.uniprot.org/core/date | "2005"xsd:gYear |
| http://purl.uniprot.org/citations/15574430 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/15574430 | http://purl.uniprot.org/core/pages | "4553-4567"xsd:string |
| http://purl.uniprot.org/citations/15574430 | http://purl.uniprot.org/core/title | "Interleukin-18 is a pro-hypertrophic cytokine that acts through a phosphatidylinositol 3-kinase-phosphoinositide-dependent kinase-1-Akt-GATA4 signaling pathway in cardiomyocytes."xsd:string |
| http://purl.uniprot.org/citations/15574430 | http://purl.uniprot.org/core/volume | "280"xsd:string |
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