Exp Mol Med.  2009 Sep;41(9):629-637. 10.3858/emm.2009.41.9.069.

Differential regulation of inducible nitric oxide synthase and cyclooxygenase-2 expression by superoxide dismutase in lipopolysaccharide stimulated RAW 264.7 cells

Affiliations
  • 1Department of Biomedical Science, College of Medicine, Hallym University, Chunchon 200-702, Korea. jinpark@hallym.ac.kr
  • 2Department of Microbiology, College of Medicine, Hallym University, Chunchon 200-702, Korea.
  • 3Research Institute for Bioscience and Biotechnology, College of Natural Sciences, Hallym University, Chunchon 200-702, Korea.

Abstract

Inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) have been known to be involved in various pathophysiological processes such as inflammation. This study was performed to determine the regulatory function of superoxide dismutase (SOD) on the LPS-induced expression of iNOS, and COX-2 in RAW 264.7 cells. When a cell-permeable SOD, Tat-SOD, was added to the culture medium of RAW 264.7 cells, it rapidly entered the cells in a dose-dependent manner. Treatment of RAW 264.7 cells with Tat-SOD led to decrease in LPS-induced ROS generation. Pretreatment with Tat-SOD significantly inhibited LPS-induced expression of iNOS and NO production but had no effect on the expression of COX-2 and PGE2 production in RAW 264.7 cells. Tat-SOD inhibited LPS-induced NF-kappaB DNA binding activity, IkappaBalpha degradation and activation of MAP kinases. These data suggest that SOD differentially regulate expression of iNOS and COX-2 in LPS-stimulated RAW 264.7 cells.

Keyword

cyclooxygenase 2; lipopolysaccharides; NF-kappaB; nitric oxide synthase type II; reactive oxygen species; superoxide dismutase

MeSH Terms

Animals
Cell Line
Cyclooxygenase 2/*genetics/metabolism
Cytokines/immunology
*Gene Expression Regulation
Lipopolysaccharides/immunology/metabolism
Mice
Mitogen-Activated Protein Kinase Kinases/metabolism
NF-kappa B/metabolism
Nitric Oxide/metabolism
Nitric Oxide Synthase Type II/*genetics/metabolism
Reactive Oxygen Species/metabolism
Superoxide Dismutase/*metabolism
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