Blockade of p38 Mitogen-activated Protein Kinase Pathway Inhibits Interleukin-6 Release and Expression in Primary Neonatal Cardiomyocytes.
- Author:
Han Jung CHAE
1
;
Hyun Ki KIM
;
Wan Ku LEE
;
Soo Wan CHAE
Author Information
1. Department of Pharmacology and Institute of Cardiovascular Research, Chonbuk National University Medical School, Jeonju, Korea. soowan@moak.chonbuk. ac.kr
- Publication Type:Original Article
- Keywords:
Interleukin-6;
p38 MAPK;
NF-kappaB;
SB203580
- MeSH:
Gene Expression;
Interleukin-6*;
Myocytes, Cardiac*;
NF-kappa B;
p38 Mitogen-Activated Protein Kinases;
Protein Kinases*
- From:The Korean Journal of Physiology and Pharmacology
2002;6(6):319-325
- CountryRepublic of Korea
- Language:English
-
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-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.
