β-Adrenergic stimulation induces interleukin-18 expression via β2-AR, PI3K, Akt, IKK, and NF-κB

Bysani Chandrasekar, Federica M. Marelli-Berg, Masahide Tone, Sailaja Bysani, Sumanth D. Prabhu, David R. Murray

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

We investigated whether β-adrenergic receptor (β-AR) stimulation induces the expression of interleukin (IL)-18, a proinflammatory cytokine, in myocardium and in cardiac-derived endothelial cells (CDEC) via activation of nuclear factor (NF)-κB. Our results indicate that isoproterenol (ISO) activates NF-κB DNA binding activity, and induces myocardial and systemic elaboration of IL-18 via β2-AR signaling. Furthermore, in CDEC, ISO increased basal and inducible promoter activities, increased IL-18 gene transcription and mRNA stability, and induced IL-18 expression via β2-AR agonism. Signaling required Gi, PI3K, Akt, IKK, and NF-κB. In conclusion, our results indicate for the first time that isoproterenol induces myocardial and systemic elaboration of IL-18 via a β2-AR and NF-κB-dependent mechanism. Similar events may occur in heart failure, a disease state characterized by sustained β-AR activation.

Original languageEnglish
Pages (from-to)304-311
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume319
Issue number2
DOIs
StatePublished - Jun 25 2004

Keywords

  • Adrenergic stimulation
  • Heart failure
  • Inflammation
  • Interleukins
  • Isoproterenol
  • NF-κB
  • Proinflammatory cytokines
  • Signal transduction

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