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UCSD research may lead to targeted treatment for asthma sufferers

The bronchial tubes of a patient with severe asthma can become scarred due to repeated episodes of allergic inflammation in the airways. The scarring results in blocked airways, excessive production of mucus, and shortness of breath.

Researchers at the University of California, San Diego (UCSD) School of Medicine have discovered that when a single gene IKK beta is selectively inactivated in the membrane-lining cells of the bronchial tubes of mice that later inhale allergens, such scarring, mucus production and airway inflammation is significantly reduced.

David H. Broide, M.B.,Ch.B., Professor in UCSD's Department of Medicine, and Michael Karin, Ph.D., Professor in UCSD's Department of Pharmacology and the Laboratory of Gene Regulation and Signal Transduction, will publish their findings in the December 6 issue of the Proceedings of the National Academy of Sciences.

"This finding is significant because it suggests that if we can produce a drug that inhibits IKK beta for example, a drug that is inhaled to target only the patient's bronchial tubes and not their immune cells then the scarring, inflammation, and mucus production in asthma could be significantly reduced," said Broide.

IKK beta is a master regulator gene that is expressed in cells throughout the body including cells lining the bronchial tubes and immune cells, which are needed to fight infection. Through its effects on the transcription factor NF-kB, IKK beta also regulates the expression of many additional genes important to the induction of airway inflammation in asthma.

Using gene-targeting strategies, the UCSD team selectively inactivated the IKK beta gene only in the mouse airway membrane-lining cells, called epithelial cells, but not in other cells outside the airway that also express the gene, such as immune cells. The researchers were able to demonstrate that mice lacking the IKK beta gene in these lining cells had significantly less airway inflammat
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Contact: Debra Kain
ddkain@ucsd.edu
619-543-6163
University of California - San Diego
29-Nov-2005


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