Abstract
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.
MeSH terms
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Animals
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Animals, Newborn
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Antigens, CD / genetics
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Antigens, CD / metabolism
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Atrial Natriuretic Factor / drug effects
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Atrial Natriuretic Factor / genetics
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Benzylamines / pharmacology
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Calcium / metabolism
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Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
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Cells, Cultured
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Cyclosporine / pharmacology
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Cytokine Receptor gp130
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Cytokines / drug effects
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Cytokines / genetics
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Egtazic Acid / pharmacology
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Endothelin-1 / metabolism*
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Endothelin-1 / pharmacology
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Gene Expression Regulation, Developmental*
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Growth Inhibitors / genetics
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Growth Inhibitors / pharmacology
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Heart / drug effects
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Heart / growth & development*
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Interleukin-6 / genetics*
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Interleukin-6 / metabolism
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Ionomycin / pharmacology
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Ionophores / pharmacology
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Leukemia Inhibitory Factor
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Lymphokines / genetics
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Lymphokines / pharmacology
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism
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Mutation
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Myocardium / cytology*
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Myocardium / metabolism
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Myosin Heavy Chains / drug effects
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Myosin Heavy Chains / genetics
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Natriuretic Peptide, Brain / genetics
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Natriuretic Peptide, Brain / metabolism
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Promoter Regions, Genetic
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Protein Kinase C / metabolism
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Protein-Tyrosine Kinases / metabolism
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Rats
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Rats, Wistar
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Sulfonamides / pharmacology
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Tetradecanoylphorbol Acetate / pharmacology
Substances
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Antigens, CD
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Benzylamines
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Cytokines
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Endothelin-1
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Growth Inhibitors
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Il6st protein, rat
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Interleukin-6
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Ionophores
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Leukemia Inhibitory Factor
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Lymphokines
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Membrane Glycoproteins
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Sulfonamides
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Natriuretic Peptide, Brain
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Cytokine Receptor gp130
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KN 93
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Egtazic Acid
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Ionomycin
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W 7
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Cyclosporine
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Atrial Natriuretic Factor
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cardiotrophin 1
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Protein-Tyrosine Kinases
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Protein Kinase C
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Calcium-Calmodulin-Dependent Protein Kinases
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Myosin Heavy Chains
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Tetradecanoylphorbol Acetate
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Calcium