A new discovery from scientists working at Trinity College Dublin could lead to a new medical cure for arthritis.
Scientists working at Trinity College Dublin have discovered a possible off-switch for inflammation, which could potentially lead to improved medical cures for the likes of arthritis, inflammatory bowel disease and heart disease.
“My lab has been exploring metabolic changes in macrophages for the past six years and we’ve come across what we think is the most important finding yet,” said Professor of Biochemistry at Trinity, Luke O’Neill. He, along with Dr. Mike Murphy of the University of Cambridge, was the joint leader of the work recently published in leading international journal Nature.
Working in the School of Biochemistry and Immunology in the Trinity Biomedical Sciences Institute at TCD, the scientists have discovered a new process within the body that can switch off inflammation. This metabolic process sees “itaconate”–a molecule derived from glucose–work powerfully against macrophages, the cells in the immune system that lie at the heart of many inflammatory diseases.
“It is well known that macrophages cause inflammation, but we have just found that they can be coaxed to make a biochemical called itaconate. This functions as an important brake or off-switch, on the macrophage, cooling the heat of inflammation in a process never before described,” Professor O’Neill continued.
It is believed that the new discovery may also help to develop much-needed new drugs to treat people living with inflammatory and infectious diseases such as arthritis, inflammatory bowel disease and heart disease.
Professor O’Neill stated: “This discovery and the new research pathways it has opened up will keep us busy for some time but we are hopeful that it will one day make a difference to patients with diseases that remain difficult to treat.”
“The macrophage takes the nutrient glucose, whose day job it is to provide energy, and surprisingly turns it into itaconate. This then blocks production of inflammatory factors, and also protects mice from the lethal inflammation that can occur during infection,” explained Dr. Evanna Mills, joint first author of the work.
“We’ve found that itaconate can directly modify a whole host of proteins important for inflammation in a chemical reaction never before described and that this reaction is important for the anti-inflammatory effects of itaconate,” added her joint first author Dylan Ryan.
The work was a collaboration with Harvard Medical School, the University of Cambridge, the University of Oxford, Johns Hopkins University, the University of Dundee, and GlaxoSmithKline, where both Professor O’Neill and Dr. Mills spent time on sabbatical.
The discoveries were made using both human cells and mice as a model organism.