Blockade of p38 mitogen-activated protein kinase pathway inhibits interleukin-6 release and expression in primary neonatal cardiomyocytes.
The induction of interleukin-6 (IL-6) using combined proinflammatory agents (LPS/IFN-gamma or TNF-alpha/IFN-gamma) was studied in relation to p38 mitogen-activated protein kinase (MAPK) and NF-kappaB transcriptional factor in primary neonatal cardiomyocytes. When added to cultures of cardiomyocytes, the combined agents (LPS/IFN-gamma or TNF-alpha/IFN-gamma) had stimulatory effect on the production of IL-6 and the elevation was significantly reduced by SB203580, a specific p38 MAPK inhibitor. SB203580 inhibited protein production and gene expression of IL-6 in a concentration-dependent manner. In this study, IFN-gamma enhancement of TNF-alpha-induced NF-kappaB binding affinity as well as p38 MAP kinase activation was observed. However, a specific inhibitor of p38 MAPK, SB203580, had no effect on TNF-alpha/IFN-gamma or LPS/IFN-gamma-induced NF-kappaB activation. This study strongly suggests that these pathways about TNF-alpha/IFN-gamma or LPS/IFN-gamma-activated IL-6 release can be primarily dissociated in primary neonatal cardiomyocytes.
Chae
H
H
Department of Dental Pharmacology, Wonkwang Dental Research Institute, School of Dentistry, Wonkwang University, Iksan Chonbuk, 570-749, South Korea.
Lee
J
J
Byun
J
J
Jung
W
W
Kwak
Y
Y
Chae
S
S
Kim
H
H
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004347:Drug Interactions; D024202:Electrophoretic Mobility Shift Assay; D007093:Imidazoles / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D015850:Interleukin-6 / Q000493:pharmacokinetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases
D007093:Imidazoles; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580