A protein that seems to play a vital role in airway function is absent in people who have asthma, according to new research. The finding points to a potential new treatment.
When the protein, called SPLUNC1, is low or missing, people experience airway constriction, mucus production, chest tightness, and breathing problems.
Robert Tarran, associate professor of medicine and a member of the University of North Carolina Marsico Lung Institute, previously associated the protein to cystic fibrosis. He and colleague Steve Tilley, associate professor of medicine at UNC-Chapel Hill, wondered what role it might play in asthmatics.
“We first measured SPLUNC1 levels in airway samples obtained from asthmatics and normal volunteers in the UNC Center for Environmental Medicine, Asthma, and Lung Biology,” Tilley says. “We were astonished to find that SPLUNC1 levels were markedly reduced in people who have asthma.”
Using mouse models that were given allergens similar to people who suffer from asthma, Tilley’s lab found that SPLUNC1 levels were depleted in the airways, similar to the findings in humans with asthma, and that restoring SPLUNC1 reversed airway hyper-responsiveness, which is a cardinal feature of asthma.
Tarran’s lab established that short palate, lung, and nasal epithelial clone 1 (SPLUNC1) could regulate airway smooth muscle contraction by preventing a calcium entry into smooth muscle cells, providing a mechanistic explanation of how a deficiency of this protein might lead to airway hyper-responsiveness.
“People have been studying SPLUNC1 and its role in the context of other diseases, such as cystic fibrosis and lung cancer, but we believe that we are the group to identify its role in asthma,” Tarran says.
Epithelial cells that line airways produce the SPLUNC1 protein.
“We found that this protein, which is actually turned off by excessive inflammation, is needed to cause the muscle to relax. It’s essentially a muscle-relaxing factor that’s missing from asthma patients. It’s something that normally acts as a brake,” Tarran says.
A potential therapy for asthma would be to replenish either the whole protein or part of the protein, which could be delivered via a nebulizer or inhaler.
“Most of the asthma therapies people use are inhalers, which have been around for decades. There have only been a few new asthma medications in the past 10 or 20 years, and they’re still being evaluated,” says Tarran. “This protein could be a potentially new target to go after, and it could really benefit a lot of people.”
The study was funded by the American Asthma Association and the National Institutes of Health.
Tongde Wu, Julianne Huang, Patrick J. Moore, Michael S. Little, William G. Walton, Robert C. Fellner, Neil E. Alexis, Y. Peter Di, Matthew R. Redinbo, Stephen L. Tilley & Robert Tarran
Identification of BPIFA1/SPLUNC1 as an epithelium-derived smooth muscle relaxing factor
Nature Communications 8, Article number: 14118 (2017) doi:10.1038/ncomms14118
Image: FDA, Michael J. Ermarth