Study points to possible cause of asthma exacerbations

the receptors for endotoxin, we found there were very low levels and they were inside the cell, not on the surface."

With that observation, the investigators wanted to see what happened to endotoxin receptors when lung cell models were infected by a virus. The team used RSV, which normally does not cause serious illness in healthy people but has epidemiological links to asthma and asthma exacerbations. They found that this virus increased both the amount and the surface expression of the receptors for endotoxin on cells lining the airway. Next, they exposed RSV-infected lung cells to endotoxin and saw the increased inflammatory response.

"The increased expression of the Toll-4 receptor after the viral infection markedly increased the sensitivity of the epithelial cells to endotoxin exposure," said Gary Hunninghake, M.D., a study author and the Sterba Professor of Internal Medicine with the UI Carver College of Medicine and a researcher and staff physician with the Iowa City VAMC.

The increased endotoxin response results in proteins that cause inflammation, constricting the airways of people with asthma. It is likely that viruses also increase the response of the airways to other environmental exposures. This increased non-specific response of asthmatic airways to environmental exposures is a typical feature of asthma, Hunninghake said.

"The next phase of these studies is to determine if viruses cause the same effect in individuals with asthma," said Hunninghake, who directs the UI Division of Pulmonary, Critical Care and Occupational Medicine and also directs the Graduate Program in Translational Biomedicine.

The team will study if the change they saw in receptor expression after RSV infection will occur in animal models of asthma and in cells taken from nasal washes of patients with asthma.

In addition to Monick and Hunninghake, the team included co-lead author Timur Yarovinsky, Ph.D., UI assistant research scientis

Contact: Becky Soglin
University of Iowa

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