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Unlocking the Immune System's Response to Infection and Injury
Date:6/16/2010

udy, Dr. Tracey and his colleagues followed the path of an important cytokine called high-mobility group box 1 (HMGB1,) a housekeeping protein that stimulates the release of other cytokines in response to infection or injury. According to the latest study, HMGB1, which is released during both infection and sterile injury, selectively binds and signals through Toll-like receptor 4 (TLR4), an essential component of the immune system that sets in motion the release of other cytokines which produce sickness syndrome. Surprisingly, they also found that the interaction between these two central proteins (HMGB1 and TLR4) requires a single cysteine, because when they substituted this amino acid for another, the signals leading to cytokine release were blocked.

“These results have implications for the rational design and development of experimental therapeutics for use in sterile and infectious inflammation, because the molecular nature of the interaction is localized to a very small region, encompassing a single amino acid,” the authors wrote. Dr. Tracey added: “This is encouraging for future clinical trials, which are needed to block HMGB1 and stop it from interacting with TLR4 in order to prevent sickness syndrome.”

About The Feinstein Institute for Medical Research: Headquartered in Manhasset, NY, The Feinstein Institute for Medical Research is home to international scientific leaders in Parkinson's disease, Alzheimer’s disease, psychiatric disorders, rheumatoid arthritis, lupus, sepsis, inflammatory bowel disease, diabetes, human genetics, leukemia, lymphoma, neuroimmunology, and medicinal chemistry. The Feinstein Institute, part of the North Shore-LIJ Health System, ranks in the top 6th percentile of all National Institutes of Health grants awarded to research centers. Feinstein researchers are developing new drugs and drug targets, and producing results where science meets the patient. For more information, please visi
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