Regulation of lipopolysaccharide-induced inflammatory response by glutathione S-transferase P1 in RAW264.7 cells

FEBS Lett. 2005 Aug 1;579(19):4081-7. doi: 10.1016/j.febslet.2005.06.034.

Abstract

Glutathione S-transferase P1(GSTP1) plays an important role in the detoxification and xenobiotics metabolism. Here, we show that GSTP1 is also involved in LPS (lipopolysaccharide)-induced inflammatory response. GSTP1 expression, determined at the transcription and translation levels, were upregulated by the LPS stimulation in RAW264.7 macrophage-like cells. GSTP1 inhibited LPS-induced mitogen-activated protein kinases MAPKs including ERK, JNK and p38 as well as NF-kappaB activation dose- and time-dependently in transient transfected and stable transfected cells. Moreover this inhibition of the signaling pathways resulted in the decrease of tumor necrosis factor alpha (TNF-alpha) and nitric oxide (NO) synthesis. These data suggest that the GSTP1 prevents LPS-induced excessive production of pro-inflammatory factors and plays an anti-inflammatory role in response to LPS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • DNA Primers
  • Enzyme Activation
  • Glutathione Transferase / metabolism*
  • Lipopolysaccharides / pharmacology*
  • Macrophages / cytology
  • Macrophages / drug effects*
  • Macrophages / enzymology
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • DNA Primers
  • Lipopolysaccharides
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Glutathione Transferase
  • Mitogen-Activated Protein Kinases