TNF-alpha and H2O2 induce IL-18 and IL-18R beta expression in cardiomyocytes via NF-kappa B activation.
Myocardial ischemia/reperfusion is characterized by oxidative stress and induction of proinflammatory cytokines. Interleukin (IL)-18, a member of the IL-1 family, acts as a proinflammatory cytokine, and is induced during various immune and inflammatory disorders. Therefore, in the present study we investigated whether IL-18 expression is regulated by cytokines and oxidative stress in cardiomyocytes. TNF-alpha induced rapid and sustained activation of NF-kappaB whereas H(2)O(2) induced delayed and transient activation. Both TNF-alpha and H(2)O(2) induced IL-18 mRNA and precursor protein in cardiomyocytes, and IL-18 release into culture supernatants. However, only TNF-alpha led to sustained expression. Expression of IL-18Rbeta, but not alpha, was induced by both agonists. TNF-alpha and H(2)O(2) induced delayed expression of IL-18 BP. Pretreatment with PDTC attenuated TNF-alpha and H(2)O(2) induced IL-18 and IL-18Rbeta, but not basal expression of IL-18Ralpha. These results indicate that adult cardiomyocytes express IL-18 and its receptors, and proinflammatory cytokines and oxidative stress regulate their expression via activation of NF-kappaB. Presence of both ligand and receptors suggests IL-18 impacts myocardial biology through an autocrine pathway.
Chandrasekar
Bysani
B
Department of Medicine/Cardiology, University of Texas Health Science Center, San Antonio 78229, USA. chandraseka@uthscsa.edu
Colston
James T
JT
de la Rosa
Sam D
SD
Rao
Perla P
PP
Freeman
Gregory L
GL
D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D020382:Interleukin-18 / Q000096:biosynthesis* / Q000235:genetics; D053728:Interleukin-18 Receptor beta Subunit; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011921:Rats, Inbred WKY; D018123:Receptors, Interleukin / Q000096:biosynthesis* / Q000235:genetics; D053724:Receptors, Interleukin-18; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation
C486426:Il18rap protein, rat; D020382:Interleukin-18; D053728:Interleukin-18 Receptor beta Subunit; D016328:NF-kappa B; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide