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Blockade of p38 Mitogen-activated Protein Kinase Pathway Inhibits Interleukin-6 Release and Expression in Primary Neonatal Cardiomyocytes  

Chae, Han-Jung (Department of Pharmacology and Institute of Cardiovascular Research, Chonbuk National University Medical School)
Kim, Hyun-Ki (Department of Pharmacology and Institute of Cardiovascular Research, Chonbuk National University Medical School)
Lee, Wan-Ku (Department of Pharmacology and Institute of Cardiovascular Research, Chonbuk National University Medical School)
Chae, Soo-Wan (Department of Pharmacology and Institute of Cardiovascular Research, Chonbuk National University Medical School)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.6, no.6, 2002 , pp. 319-325 More about this Journal
Abstract
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 $NF-{\kappa}B$ 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 $TNF-{\alpha}-induced\;NF-{\kappa}B$ binding affinity as well as p38 MAP kinase activation was observed. However, a specific inhibitor of p38 MAPK, SB203580, had no effect on $TNF-{\alpha}/IFN-{\gamma}\;or\;LPS/IFN-{\gamma}-induced\;NF-{\kappa}B$ 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.
Keywords
Interleukin-6; P38 MAPK; $NF-_{\kappa}B$; SB203580;
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