Researchers at the Johns Hopkins Bloomberg School of Public Health and other institutions have identified a "master gene" in mice that controls the action of 50 other genes whose products protect the lungs against environmental pollutants. The researchers believe their findings will provide a better understanding of the human body's defense mechanisms and could lead to the identification of what factors make some people more susceptible to lung diseases. The article is published in the current issue of The Journal of Clinical Investigation.

The so-called "master gene"--nuclear factor erythroid-derived 2-related factor 2 (Nrf2)--is activated in response to environmental pollutants such as cigarette smoke, and then turns on numerous antioxidant and pollutant-detoxifying genes to protect the lungs from developing emphysema.

Shyam Biswal, PhD, senior author of the study and an assistant professor in the Bloomberg School of Public Health's Department of Environmental Health Sciences, said, "The important thing to remember is that the degree of lung damage depends on the ability to defend against environmental factors. We now know that Nrf2 is the key player in protection even in the case of chronic exposure to pollutants."

In 2002, Dr. Biswal and colleagues were the first to show that activation of Nrf2 in response to an anticancer agent--Sulforaphane--can turn on antioxidant genes, but little was known about Nrf2-regulated genes and their role in lung inflammatory diseases caused by chronic exposure to environmental agents. By exposing mice to cigarette smoke, the researchers were able to learn which gene controlled this natural defense mechanism.

The researchers found that disruption of the Nrf2 gene caused earlier onset and more severe emphysema in a strain of mice that is resistant to cigarette smoke-related emphysema.Through gene chip analysis, the researchers were able to identify 50 Nrf2-dependent antioxidant and cytoprotective pulm
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Contact: Kenna L. Lowe
paffairs@jhsph.edu
410-955-6878
Johns Hopkins University Bloomberg School of Public Health
1-Nov-2004

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