No effective treatment exists for acute lung injury, but a team
of UB researchers, including Brahm H. Segal, MD, may help change
that.
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
condition.
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.
They found that both limit acid aspiration-induced acute lung
injury, but through distinct mechanisms, says Brahm
H. Segal, MD, professor of medicine.
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.
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