The Regulatory Role Of Glutathione S-transferase P1 In LPS- And TNF-α-induced Signaling Pathways

Human glutathione S-transferase P1 is a ubiquitous expressed protein which plays an important role in the detoxification and xenobiotics metabolism. Previous studies show that GSTP1 is a cancer marker and associates with anticancer drug resistance. It has also shown that GSTPl interacts with c-Jun NH2-terminal kinase (JNK) and suppresses its activity. In the present study, we report that GSTP1 regulates the lipopolysaccharide (LPS)-induced inflammatory response and TNF-α-triggered signaling pathways.Firstly, we show that GSTP1 is involved in LPS-induced inflammatory response. GSTP1 expression, determined at the transcription and translation levels, were upregulated by the LPS stimulation in RAW264.7 macrophage-like cells. Overexpression of GSTP1 inhibited LPS-induced mitogen-activated protein kinases (MAPKs) including ERK, JNK and p38 as well as NF-κB activation dose- and time-dependently in transient transfected and stable transfected cells. Moreover, this inhibition of the signaling pathways results in the decrease of tumor necrosis factor alpha (TNF-α) and nitric oxide (NO) syntheses. These data suggest that GSTP1 prevents LPS-induced excessive production of pro-inflammatory factors and plays an anti-inflammatory role in response to LPS.TNF-α is a pleiotropic cytokine that elicits a wide spectrum of physiological and pathogenic events including cell proliferation, differentiation, apoptosis and...