The allergen breathed in by a person with asthma triggers a proteinase or enzyme called MMP7 that activates a cascade of events to prompt an allergic reaction, said a consortium of researchers led by Baylor College of Medicine in Houston in a report that appears online March 29 in the journal Nature Immunology.
In particular, MMP7 activates interleukin 25, a key mediator of the allergic response in the lung said Drs. Farrah Kheradmand and David B. Corry, associate professors of medicine-pulmonary at BCM, and senior authors of the report.
In the same report, the researchers report that they have identified a form of vitamin A made in the lung that is critical for dampening the inflammatory effect. Mice that lack MMP7 were found to have higher production of retinal dehydrogenase, an enzyme that is responsible for synthesizing vitamin A in the lung. MMP7 deficient mice showed less lung inflammation when they are exposed to allergens than did mice who had enough MMP7. Suppressing the production of vitamin A restored the asthmatic symptoms in the MMP7 deficient mice.
"It is important to know which mediators in the airway may be setting off the initial cascade of events that result in the asthmatic reaction in the lung; it would be like getting to the top of the food chain," they said.
In the future, they said, they hope to identify the relationship between the synthesis of vitamin A in the body and the repression of MMP7.
Others who took part in this work include Sangeeta Goswami, Ming Shan, Wade T. Barranco, Sumanth Polikepahad, Alexander Seryshev and Li-Zhen Song, all of BCM; Pornpimon Angkasekwinai and Chen Dong of The University of Texas M.D. Anderson Cancer Center in Houston; Kendra J. Greenlee of North Dakota State University in Fargo; David Redding, Bhupinder Singh and Sanjiv Sur of U.T. Medical Branch in Galveston, and Prescott Woodruff of the University of California, San Francisco.
Funding for this comes from the National Institutes of Health, the American Lung Association, the Leukemia and Lymphoma Society and The UT MD Anderson Cancer Center.
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