Endothelin-1 induces expression of fetal genes through the interleukin-6 family of cytokines in cardiac myocytes.
We here examined the role of the interleukin-6 (IL-6) family of cytokines in endothelin-1 (ET-1)-induced hypertrophic responses using cultured cardiac myocytes of neonatal rats. ET-1 induced expression of IL-6 and leukemia inhibitory factor (LIF) genes. ET-1-induced LIF gene expression was abolished by inhibition of protein kinase C activity. ET-1 activated the promoter of atrial natriuretic peptide and beta-type myosin heavy chain genes through the tyrosine kinase pathway and IL-6 receptor gp130. These results suggest that the IL-6 family of cytokines mediates ET-1-induced expression of some fetal genes in cardiac myocytes.
Saito
S
S
Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Japan.
Aikawa
R
R
Shiojima
I
I
Nagai
R
R
Yazaki
Y
Y
Komuro
I
I
D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D009320:Atrial Natriuretic Factor / Q000187:drug effects / Q000235:genetics; D001596:Benzylamines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D050822:Cytokine Receptor gp130; D016207:Cytokines / Q000187:drug effects / Q000235:genetics; D004533:Egtazic Acid / Q000494:pharmacology; D019332:Endothelin-1 / Q000378:metabolism* / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D006131:Growth Inhibitors / Q000235:genetics / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000254:growth & development*; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000235:genetics / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000187:drug effects / Q000235:genetics; D020097:Natriuretic Peptide, Brain / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D000096926:Benzenesulfonamides
D015703:Antigens, CD; D009320:Atrial Natriuretic Factor; D001596:Benzylamines; D002118:Calcium; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D016572:Cyclosporine; D050822:Cytokine Receptor gp130; D016207:Cytokines; D004533:Egtazic Acid; D019332:Endothelin-1; D006131:Growth Inhibitors; D015850:Interleukin-6; D015759:Ionomycin; D007476:Ionophores; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D008562:Membrane Glycoproteins; D018995:Myosin Heavy Chains; D020097:Natriuretic Peptide, Brain; D011493:Protein Kinase C; D011505:Protein-Tyrosine Kinases; D013449:Sulfonamides; D013755:Tetradecanoylphorbol Acetate; C494201:Il6st protein, rat; C072105:KN 93; D000096926:Benzenesulfonamides; C017967:W 7; C092073:cardiotrophin 1