RIS ID
118181
Abstract
Glutathione transferase Omega 1 (GSTO1-1) is an atypical GST reported to play a pro-infammatory role in response to LPS. Here we show that genetic knockout of Gsto1 alters the response of mice to three distinct infammatory disease models. GSTO1-1 defciency ameliorates the inflammatory response stimulated by LPS and attenuates the infammatory impact of a high fat diet on glucose tolerance and insulin resistance. In contrast, GSTO1-1 defcient mice show a more severe inflammatory response and increased escape of bacteria from the colon into the lymphatic system in a dextran sodium sulfate mediated model of infammatory bowel disease. These responses are similar to those of TLR4 and MyD88 defcient mice in these models and confrm that GSTO1-1 is critical for a TLR4-like pro-infammatory response in vivo. In wild-type mice, we show that a small molecule inhibitor that covalently binds in the active site of GSTO1-1 can be used to ameliorate the infammatory response to LPS. Our fndings demonstrate the potential therapeutic utility of GSTO1-1 inhibitors in the modulation of infammation and suggest their possible application in the treatment of a range of inflammatory conditions.
Grant Number
NHMRC/1124673
Publication Details
Menon, D., Innes, A., Oakley, A. J., Dahlstrom, J. E., Jensen, L. M., Brustle, A., Tummala, P., Rooke, M., Casarotto, M. G., Baell, J. B., Nguyen, N., Xie, Y., Cuellar, M., Strasser, J., Dahlin, J. L., Walters, M. A., Burgio, G., O'Neill, L. A. J. & Board, P. G. (2017). GSTO1-1 plays a pro-inflammatory role in models of inflammation, colitis and obesity. Scientific Reports, 7 17832-17832.