Researchers Identify Protein Relevant to COPD

A report published in The Journal of Clinical Investigation claimed smoking causes the destruction of a key immune protein in the lungs, which the researchers believe is linked to chronic obstructive pulmonary disease (COPD) development.

A team from Brown University extracted mRNA from the lung tissues of patients with (n=36) and without (n=7) COPD. By looking at COPD patients who currently and formerly smoked, they found a disparity in levels of a protein called NLRX1.

Moreover, an analysis of three groups of individuals showed NLRX1 expression was lower in people with COPD and correlated with the disease’s severity.

“We observed that the levels of this molecule could explain diverse aspects of disease severity and patient’s symptoms,” lead author Min-Jong Kang, a researcher at Yale and Brown, said in a statement.

In COPD patients, the authors claimed lung degradation is caused by an erroneous response in the MAVS/RIG-I-like helicase pathway, a mitochondrial immune pathway which job is to fight off viruses. Their study found NLRX1 doesn’t curb the pathway’s effects, but prevents it from activating incorrectly in the first place. The team also implicated smoking’s role, which they claimed severely impacted the protein’s prevalence.

Mice were used to gain more insight into NLRX1 and cigarette smoke’s (CS) role in COPD development. For the first part of their experiment, mice exposed to CS were found to have significantly lower NLRX1 levels than controls.

“Taken together, these results suggest that NLRX1 is a critical inhibitor of CS-induced pulmonary inflammation and tissue remodeling responses and that its inhibitory functions are decreased in pulmonary tissues by chronic cigarette smoke (CS) exposure,” the authors wrote.

Furthermore, in mice with elevated NLRX1 levels, the investigators reported they were able to successfully stop the MAVS/RIG-like helicase immune response. Given their findings, they believe NLRX1 not only paves the way for effective COPD treatments, but also could act as a predictor of COPD progression.

“This is a new school of thought in terms of what causes emphysema and a new school of thought regarding how CS does what it does,” corresponding author Jack A. Elias, a pulmonologist and dean of medicine and biological sciences at Brown University, said in the statement. “We’re showing that a lot of what’s going on is related to mitochondria.”