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No effective treatment exists for acute lung injury, but a team of UB researchers, including Brahm H. Segal, MD, may help change that.

Immune Pathways Suggest Target for Treating Acute Lung Injury

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 condition.

New UB research may pave the way to clinical trials that evaluate targeting Nrf2 as a therapeutic or prevention approach to limit acute lung injury.

Protective Pathways, Distinct Mechanisms

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.

Transcription Factor Nrf2 is Potential Target

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.

Paper Published in Journal of Immunology

Segal has been exploring both NADPH oxidase and Nrf2 as key mediators of acute inflammation and injury.

His colleagues in anesthesiologyBruce 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.