Published February 14, 2013
UB researchers have identified specific roles for two innate
immune pathways that drive acute lung injury–findings that
may lead to the first treatment or preventive strategy for the
Using genetically engineered mice, the research team studied
NADPH oxidase, a membrane-bound enzyme complex that generates
reactive oxidants to kill bacteria and fungi. They also looked at
Nrf2, a transcription factor induced by these oxidants which, in
turn, induces pathways that limit oxidant stress and injury.
In addition, researchers found that an agent that activities Nrf2—a synthetic triterpenoid known as CDDO-Im—protected mice from acute lung injury.
The research may pave the way to clinical trials that evaluate
targeting Nrf2 as a therapeutic or prevention approach to limit
acute lung injury.
Aside from supportive care, no effective treatment exists for acute lung injury, which can be caused by various conditions, including sepsis, pneumonia and acid aspiration, explains Segal, who is also chief of infectious diseases at Roswell Park Cancer Institute.
If acute lung injury progresses to respiratory failure, it has a
high fatality rate.
Segal has been exploring both NADPH oxidase and Nrf2 as key mediators of acute inflammation and injury.
His colleagues in anesthesiology—Bruce A. Davidson, PhD, basic science research coordinator, and Paul R. Knight III, MD, PhD, Distinguished Professor of Anesthesiology and Microbiology—have been studying mechanisms of gastric aspiration-induced acute lung injury.
Their paper was published online Jan. 7 in the Journal of Immunology. Davidson is first author and Segal is the senior/corresponding author. Knight and Barbara A. Mullan, a research technician in anesthesiology, are co-authors.
Other co-authors are from Roswell Park, the University of Michigan, Vanderbilt University, the University of Alabama at Birmingham, Dartmouth Medical School and Beth Israel Deaconess Medical Center.