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Study points to possible cause of asthma exacerbations

Researchers know that viral infections can exacerbate asthma and, in turn, make people with the condition more sensitive to environmental exposures such as endotoxin. But how viral infections contribute to this sensitivity in airway cells has not been clear. A recent study led by investigators from the University of Iowa Roy J. and Lucille A. Carver College of Medicine and the Veterans Affairs Medical Center (VAMC) in Iowa City shows, for the first time, that viral infections may increase environmental sensitivity in lung epithelial (surface) cells by changing expression of receptors on those cells.

Using cell models, the team specifically showed that respiratory syncytial virus (RSV) infection increases the number of a type of receptor called Toll-4 on the airway cells. This Toll-4 receptor can provide a foothold for inhaled endotoxin, a naturally occurring environmental contaminant that comes from bacteria and is found in household dust, grain dust and objects such as pillows. The presence of receptors for endotoxin would lead to interaction between the epithelial cell and the endotoxin and potentially cause inflammation. The study appeared in the December 26, 2003, issue of the Journal of Biological Chemistry.

"The big picture here is that viral infections may upregulate, or increase, one or more receptors on the airway cells and make them more sensitive to environmental exposures. This could explain the viral-induced asthma exacerbations seen in people with asthma," said Martha Monick, senior research assistant in the Division of Pulmonary, Critical Care and Occupational Medicine in the UI Department of Internal Medicine and the study's co-lead author.

Monick said the inspiration for the study came when the team put endotoxin on normal airway epithelial cells and noticed there was no inflammatory response.

"This puzzled us, so we started thinking about receptors on lung cells," Monick said. "When we looked in normal lung cells for
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Contact: Becky Soglin
becky-soglin@uiowa.edu
319-335-6660
University of Iowa
24-Mar-2004


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