Possible Off Switch For Inflammation5 months, 2 weeks ago
Posted on Apr 07, 2018, 2 a.m.
Scientists may have discovered a promising off switch for overactive immune cells of many inflammatory diseases such as IBD, heart disease, and arthritis. Scientists are now keen on investigating whether or not the findings can be exploited to develop new anti-inflammatory medicines, as published in the international journal Nature.
Itaconate is a molecule derived from glucose that seems to act as an off switch for macrophages which are the cells in the immune system that are key to many inflammatory diseases, and is hoped will have relevance in inflammatory and infectious disease as well as drugs to treat the conditions. Discovery was made using mice model and human cells.
Macrophages take the nutrient glucose and turn it into itaconate which blocks production of inflammatory factors and can protect from then inflammation that can occur during infection. Itaconate is able to directly modify proteins important to inflammation in a never described before chemical reaction which are important for the anti-inflammatory effects of itaconate.
This work was done in collaboration with the University of Cambridge, University of Oxford, University of Dundee, Johns Hopkins University, GlaxoSmithKline, and Harvard Medical School. The new research and discovery and pathways they have opened will be keeping the researchers busy, they are hopeful that their work will make a difference to help patients will diseases that are difficult to treat effectively.
Materials provided by Trinity College Dublin.
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Evanna L. Mills, Dylan G. Ryan, Hiran A. Prag, Dina Dikovskaya, Deepthi Menon, Zbigniew Zaslona, Mark P. Jedrychowski, Ana S. H. Costa, Maureen Higgins, Emily Hams, John Szpyt, Marah C. Runtsch, Martin S. King, Joanna F. McGouran, Roman Fischer, Benedikt M. Kessler, Anne F. McGettrick, Mark M. Hughes, Richard G. Carroll, Lee M. Booty, Elena V. Knatko, Paul J. Meakin, Michael L. J. Ashford, Louise K. Modis, Gino Brunori, Daniel C. Sévin, Padraic G. Fallon, Stuart T. Caldwell, Edmund R. S. Kunji, Edward T. Chouchani, Christian Frezza, Albena T. Dinkova-Kostova, Richard C. Hartley, Michael P. Murphy, Luke A. O’Neill. Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1. Nature, 2018; DOI: 10.1038/nature25986