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

Glutathione S-transferase P1(GSTP1) plays an important role in the detoxification and xenobioties 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-kappa B 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. (c) 2005 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.