Asthma is a complex inflammatory disease of the airway characterized by airway inflammation and hyperreactivity. The incidence of asthma has doubled in the past two decades in the United States, affecting 20 million Americans. Controlling inflammation is a focus of asthma therapy. Inflammation occurs when certain cells migrate into the airways. These "inflammatory" cells release reactive oxygen species (ROS), causing the airway lining to swell and restrict. ROS is thought to cause lung tissue damage as well. ROS levels are normally offset by antioxidants in non-asthmatics. Recently, researchers have been hunting for novel genes that regulate inflammation with the hope of developing them as targets for the next generation of asthma drugs.
Suspecting that a defect in antioxidant response exacerbates asthma severity, the team of researchers began looking into the genetic factors that might contribute to this deficiency. In 2002, Biswal's lab discovered Nrf2 acts as a master regulator of the majority of antioxidant pathways and detoxifying enzymes for environmental pollutants. This led researchers to consider the role of Nrf2 in lung inflammatory diseases caused by exposure to allergens. They found that the absence of the Nrf2 gene increased migration of inflammatory cells into the airways and caused an enhanced asthmatic response in mice. "Nrf2 is critical for proper response to allergens in lungs and maintenance of a balance between ROS production. Antioxidant capability regulated by Nrf2 may be a major determina
Contact: Tim Parsons
Johns Hopkins University Bloomberg School of Public Health