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U Iowa study identifies damaging mechanism in transplants and heart attacks

A University of Iowa study suggests that inhibiting a certain protein involved in inflammation might be of therapeutic benefit in organ transplantation, heart attacks and possibly stroke. The study, led by John Engelhardt, Ph.D., UI professor and interim head of anatomy and cell biology, found that blocking the action of this protein can prevent the tissue damage caused by ischemia/reperfusion injury. The study is published in the March 1 issue of the Journal of Clinical Investigation.

Ischemia/reperfusion injury is a common, damaging component of organ transplantation, heart attack, and stroke and is a determinant of organ failure in all cases. In this type of injury, the organ is initially deprived of oxygen-carrying blood (ischemia). During reperfusion (the re-establishment of blood supply), toxins are briefly generated from the oxygen that lead to tissue damage and trigger a potentially detrimental inflammatory response.

Although inflammation is an important bodily response to environmental injuries including bacterial and viral infection as well as ischemia/reperfusion injury, too much inflammation can damage healthy tissue and cause problems.

"In this study we looked at a well-known 'master switch' type of protein called NF-kB that controls the expression of genes that regulate inflammatory responses," said Engelhardt, who also is professor of internal medicine in the UI Roy J. and Lucille A. Carver College of Medicine and director of the UI Center for Gene Therapy of Cystic Fibrosis and Other Genetic Diseases.

Engelhardt and his colleagues, including graduate student and lead author of the study, Chenguang Fan, compared the activation of NF-kB in response to bacterial infection and ischemia/ reperfusion injury. Historically, these two types of injury were thought to produce inflammation via the same cellular pathway. However, the UI researchers found that there are two distinct pathways for the two different types of i
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Contact: Jennifer Brown
jennifer-l-brown@uiowa.edu
319-335-9917
University of Iowa
1-Mar-2004


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