Beta-adrenergic stimulation induces interleukin-18 expression via beta2-AR, PI3K, Akt, IKK, and NF-kappaB.

Academic Article

Abstract

  • We investigated whether beta-adrenergic receptor (beta-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)-kappaB. Our results indicate that isoproterenol (ISO) activates NF-kappaB DNA binding activity, and induces myocardial and systemic elaboration of IL-18 via beta2-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 beta2-AR agonism. Signaling required GiPI3K, PI3K, Akt, IKK, and NF-kappaB. In conclusion, our results indicate for the first time that isoproterenol induces myocardial and systemic elaboration of IL-18 via a beta2-AR and NF-kappaB-dependent mechanism. Similar events may occur in heart failure, a disease state characterized by sustained beta-AR activation.
  • Authors

    Keywords

  • Adrenergic beta-Agonists, Animals, Cells, Cultured, Gene Expression Regulation, I-kappa B Kinase, Interleukin-18, Isoproterenol, Male, Mice, Mice, Inbred C57BL, Myocardium, NF-kappa B, Phosphatidylinositol 3-Kinases, Promoter Regions, Genetic, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-akt, Receptors, Adrenergic, beta-2
  • Digital Object Identifier (doi)

    Author List

  • Chandrasekar B; Marelli-Berg FM; Tone M; Bysani S; Prabhu SD; Murray DR
  • Start Page

  • 304
  • End Page

  • 311
  • Volume

  • 319
  • Issue

  • 2