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Study detects immunity protein that increases inflammation

Study detects immunity protein that increases inflammationA recent study by scientists at the University Of Pittsburgh School Of Medicine have discovered a new biological pathway of immunity that ramps up inflammation and then identified the agents that can block it. It is possible this may lead to increased survival and improved lung function.

Senior author Dr. Rama Mallampalli said that pneumonia and other infections can sometimes provoke an inflammatory response from the body and this is more damaging than the disease-causing bacteria. Dr. Mallampalli discovered during ongoing studies that infecting bacteria activates a previously unknown protein called Fbxo3 to form a complex which degrades another protein called Fbxl2. Fbxl2 is needed to supress the inflammatory response. This results in an exaggerated inflammatory response that can lead to further lung tissue damage, multi-organ failure and shock.

The research team carrying out these experiments, led by Dr. Bill B. Chen, observed that mice lacked the ability to make Fbxo3 if they were infected by a strain of Pseudomonas bacteria. It was also discovered that they have better lung mechanics and longer survival than mice that still made the protein.

Research members Dr. Byran McVerry and Dr. Yingze Zhang found that blood samples from 16 people who had sepsis, a condition in which the body fights a severe infection which has spread via the bloodstream, revealed higher levels of Fbxo3 and other inflammatory proteins and lower levels of Fbxl2. Based on the structure of Fbxo3, a family of small molecules was developed by the researchers, with the aim of inhibiting its activity the researchers developed. The administration of one of them, called BC-1215, led to inflammatory markers being reduced and improved lung mechanics in mouse models of pneumonia and sepsis.

Dr. Mark T. Gladwin, chief of the Division of Pulmonary, Allergy and Critical Care Medicine at Pitt School of Medicine, states that this is the key to finding ways to help the body work with its inflammatory responses to allow it to kill infectious agents without causing injury to healthy tissue. He says “the F-box protein Fbxo3, and other related proteins, represent ideal targets for treatment of acute lung injury, because it controls the innate immune response, is upstream of important inflammatory signalling pathways, and is more selective than traditional drugs that regulate protein turnover,”

The team is beginning to study the effects of BC-125 on other conditions of systemic inflammation, such as colitis and arthritis.

Reference: www.sciencedaily.com

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Randox offers a number of arrays which contains proteins which are increasingly associated with inflammation. For example, the Cerebral Array II from Randox contains the C-reactive protein (CRP) assay, while Adhesion Arrays contain assays from the Selectin family. Altered levels of adhesion molecules can be markers of inflammation as well as diabetes and cardiovascular disease.

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