GSTO1-1 plays a pro-inflammatory role in models of inflammation, colitis and obesity

Deepthi Menon, Ashlee Innes, Aaron J. Oakley, Jane E. Dahlstrom, Lora M. Jensen, Anne Brüstle, Padmaja Tummala, Melissa Rooke, Marco G. Casarotto, Jonathan B. Baell, Nghi Nguyen, Yiyue Xie, Matthew Cuellar, Jessica Strasser, Jayme L. Dahlin, Michael A. Walters, Gaetan Burgio, Luke A.J. O'Neill, Philip G. Board

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38 Scopus citations


Glutathione transferase Omega 1 (GSTO1-1) is an atypical GST reported to play a pro-inflammatory role in response to LPS. Here we show that genetic knockout of Gsto1 alters the response of mice to three distinct inflammatory disease models. GSTO1-1 deficiency ameliorates the inflammatory response stimulated by LPS and attenuates the inflammatory impact of a high fat diet on glucose tolerance and insulin resistance. In contrast, GSTO1-1 deficient 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 inflammatory bowel disease. These responses are similar to those of TLR4 and MyD88 deficient mice in these models and confirm that GSTO1-1 is critical for a TLR4-like pro-inflammatory 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 inflammatory response to LPS. Our findings demonstrate the potential therapeutic utility of GSTO1-1 inhibitors in the modulation of inflammation and suggest their possible application in the treatment of a range of inflammatory conditions.

Original languageEnglish (US)
Article number17832
JournalScientific reports
Issue number1
StatePublished - Dec 1 2017

Bibliographical note

Funding Information:
This work was supported by a grant from the Gretel and Gordon Bootes Medical Research Foundation to D.M. and P.B. The National Health and Medical Research Council of Australia (NHMRC) is thanked for Project Grant APP1124673 to PB, MC, LO, AO, and Fellowship support for J.B. (2012–2016 Senior Research Fellowship #1020411). J.B. acknowledges the Australian Federal Government Education Investment Fund Super Science Initiative and the Victorian State Government, Victoria Science Agenda Investment Fund for infrastructure support, and Translating Health Discovery (THD) NCRIS soft infrastructure support through Therapeutic Innovation Australia (TIA).

Publisher Copyright:
© 2017 The Author(s).


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