TY - JOUR
T1 - β-Adrenergic stimulation induces interleukin-18 expression via β2-AR, PI3K, Akt, IKK, and NF-κB
AU - Chandrasekar, Bysani
AU - Marelli-Berg, Federica M.
AU - Tone, Masahide
AU - Bysani, Sailaja
AU - Prabhu, Sumanth D.
AU - Murray, David R.
N1 - Funding Information:
This work was supported in part by National Institutes of Health Grant HL68020 to B.C. S.D.P. is supported by a Veterans Administration merit grant and NIH PO1 ES011860-01A1. We thank Dr. Gregory L. Freeman for his helpful discussions and criticism of the manuscript.
PY - 2004/6/25
Y1 - 2004/6/25
N2 - 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.
AB - 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.
KW - Adrenergic stimulation
KW - Heart failure
KW - Inflammation
KW - Interleukins
KW - Isoproterenol
KW - NF-κB
KW - Proinflammatory cytokines
KW - Signal transduction
UR - http://www.scopus.com/inward/record.url?scp=2642562761&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2004.04.185
DO - 10.1016/j.bbrc.2004.04.185
M3 - Article
C2 - 15178407
AN - SCOPUS:2642562761
SN - 0006-291X
VL - 319
SP - 304
EP - 311
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -