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Protein involved in cystic fibrosis also plays role in emphysema, chronic lung disease
Date:12/29/2010

esearchers analyzed CFTR and ceramide levels in lung tissue obtained from non-smokers and from light and heavy former or current smokers. To further explore the link between cigarette smoke, CFTR and ceramide, the researchers compared lung tissue from mice with "virgin" lungs never exposed to smoke to tissue from the lungs of mice exposed to cigarette smoke for five hours a day over five days. The lungs of smoke-exposed mice had decreased CFTR expression and increased ceramide levels, thus confirming the role of cigarette smoke in lung damage. The heavier the smoking, the greater the lung damage, the lower the CFTR expression and the higher the ceramide accumulation, the researchers noted, clearly linking CFTR and ceramide levels to smoking history and disease severity.

Beyond clarifying the link between CFTR, ceramide and lung damage, the Hopkins team explained just how CFTR causes ceramide to trigger lung-damaging inflammation. Analyzing lung cells from people and mice lacking CFTR in their cell membrane under a microscope and with a technique called flow cytometry that captures changes in inflammatory and protein markers, the scientists noticed increased clustering of ceramide molecules on sections of the cell membrane called lipid rafts, known to be hot spots where inflammatory signaling proteins congregate. This clustering, the researchers said, leads to increased inflammatory signaling, greater inflammation and cell damage, but cells with normal CFTR had no such clustering. Apparently, the researchers say, when functioning properly CFTR keeps a lid on the signaling activity of inflammatory receptors by preventing them from clustering, thus warding off inflammation and lung damage.

"We anticipate that membrane CFTR and ceramide may turn out to be useful predictors of susceptibility to lung damage from smoking and infections and may be tailored for drug therapy to alter disease course," Vij said.

To further test their hypothesis, the resea
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Contact: Ekaterina Pesheva
epeshev1@jhmi.edu
410-516-4996
Johns Hopkins Medical Institutions
Source:Eurekalert  

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