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Stressed out and asthmatic
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     The ability to cope with stress may decrease susceptibility to asthma, according to Rangasamy and colleagues on page 47. The absence of the transcription factor Nrf2, which helps cells respond to oxidative stress, exacerbated allergic responses in mice, leading senior author Shyam Biswal to speculate that inducers of the Nrf2 pathway may have therapeutic potential for the treatment of human asthma.

    Influx of eosinophils (brown) into the lungs is increased in the absence of the transcription factor Nrf2 (bottom).

    Asthma is a complex disorder that involves the recruitment of inflammatory cells, including eosinophils, to the lungs. Once there, these cells release reactive oxygen species (ROS), which are thought to contribute to lung tissue damage. Levels of ROS are normally counterbalanced by antioxidants, which are present at lower levels in the airways of asthma patients.

    Here, Rangasamy and colleagues investigated the effect of oxidative stress on asthma in mice lacking Nrf2, which induces the expression of many antioxidant genes. They found that the lack of Nrf2 increased influx of cells into the airways, mucus production, airway hypersensitivity, and T helper 2 cytokine production—all characteristic symptoms of asthma—in response to challenge with an inhaled allergen.

    Although the mechanisms involved remain largely unknown, the elevated cytokine levels likely resulted from increased activation of NF-B, which is known to be activated by ROS. They now plan to look for alterations in the Nrf2 gene in asthma-prone humans, as they think defects in this gene might contribute to susceptibility to disease.(Heather L. Van Epps)