In general, hyper-responsiveness doesn't seem like a bad trait; it's certainly something you'd like from your cell phone company. But in the lungs, hyper-responsiveness is a major hallmark of asthma, a condition wherein the airways inflame and restrict breathing. Researchers at the University of North Carolina School of Medicine believe they may have found a protein that can combat this extreme reaction of the lungs, which could one day wind up in an inhaler to help asthmatics regain normal respiratory function in the face of an attack.
The protein is known as SPLUNC1 and UNC researchers first identified it as playing a role in cystic fibrosis, then wondered if it might have a positive role to play in asthma. Sure enough, when they tested asthmatics, they found significantly reduced levels of the protein.
It turns out SPLUNC1, which is produced by the epithelial cells lining the airways, is able to prevent calcium from entering into the smooth muscle cells found there, thereby keeping them from contracting and causing the hyper-responsive reaction involved in an asthma attack. In short, it acts as a muscle relaxant.
"We found that this protein, which is actually turned off by excessive inflammation, is needed to cause the muscle to relax," said Robert Tarran, PhD, associate professor of medicine, and a member of the UNC Marsico Lung Institute who was involved in the study. "It's essentially a muscle-relaxing factor that's missing from asthma patients. It's something that normally acts as a brake."
The researchers say that they've decoded the crystal structure of the protein and determined which part of it is responsible for working with the smooth muscle cells. Knowing this, they say, could help them develop a new kind of inhaler that would introduce either the whole SPLUNC1 protein or its active part back into asthmatics to help alleviate symptoms. Tarran and his colleague Steve Tilley, UNC associate professor of medicine have applied for a grant from the National Institutes of Health to study the possibility further.
"We want to study this in patients to correlate SPLUNC1 levels with airway hyper-reactivity," Tarran said. "And we also want to go deeper into the mechanism – how does this protein do what we observed. So there are several future avenues of research: expanding clinical studies, designing drugs in mouse studies, and then studying the underlying biology of what happens in a person with asthma."
If mouse trials are any indication, the treatment holds hope. In their research, Tilley's lab induced allergic reactions in mice that were similar to an asthma attack. They indeed found that SPLUNC1 levels were reduced during the flare up, and that introducing the protein to the animals reversed the hyper-responsiveness of the lungs.
The research has been published in the journal Nature Communications.
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