( um of genes used by the host to defend ...)Researches discover gene critical for protection against septic-shock-induced death

Biswal's team found that the deletion of the Nrf2 gene increased the inflammatory response and caused early death in mice subjected to septic peritonitis or endotoxin shock or both. Mice deficient in Nrf2 gene expressed dramatically increased levels of effector molecules (cytokines) that mediate innate immune response, the body's first line of defense. "Sepsis syndrome is like a speeding car with a brake failure. Nrf2 may function like a brake that regulates the speed," said Biswal, senior author of the study and assistant professor in the Bloomberg School's Department of Environmental Health Sciences. Biswal speculates that suboptimal function of Nrf2 may be one reason why some intensive-care patients progress into severe sepsis and die.

"Nrf2 protects from septic shock by two mechanisms," explained lead author Rajesh Thimmulappa, PhD, a postdoctoral fellow at Environmental Health Sciences, Bloomberg School of Public Health. "First, Nrf2 protects from dysregulation of host inflammatory response, which is a characteristic feature of septic shock. Secondly, Nrf2 protects from oxidative pathological damage, the main cause of multi-organ failure during septic shock. Hence, Nrf2 can be a promising therapeutic target for attenuating septic-related deaths."

According to Biswal, the findings provide a better understanding of the human body's defense mechanisms to sepsis and septic shock, and may provide clues to designing novel therapies that could minimize mortality. The researchers are now trying to find if activation of Nrf2 by a small-molecule drug can minimize pathological damage and improve survival during sepsis caused by bacteria or viruses. Future studies will determine the therapeutic potential of targeting Nrf2 for treatment of sepsis and other
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Source:Johns Hopkins University Bloomberg School of Public Health