Researchers at Duke University have identified how nanoparticles from diesel exhaust damage lung airway cells, a finding that could lead to new therapies for people susceptible to airway disease. The researchers also discovered that the severity of the injury depends on the genetic make-up of the affected individual, according to the findings published in the journal Environmental Health Perspectives.

Diesel exhaust particles, a major part of urban smog, consist of a carbon core coated with organic chemicals and metals. The researchers showed that the particle core delivers these organic chemicals onto brush-like surfaces called cilia, which clear mucus from the airway lining. Contact with these chemicals then triggers a “signaling cascade,” as the cells respond.
In some patients, who have a single “letter” difference in their DNA, a circuit called the TRPV4 ion channel signals more strongly in response to the pollutants. Previous research showed that this gene variant makes humans more liable to develop chronic obstructive pulmonary disease (COPD).

The findings of this study show that about 75% of people have the version of the gene MMP-1 that leads to greater production of the molecule MMP-1 mediator, which destroys lung tissue. This genetic make-up allows for a turbo-charged production of MMP-1, which damages airways and lungs at multiple levels. According to the researchers, a more fortunate 25% of people escape this high level of production of MMP-1, which may be reflected in the fact that certain individuals can better manage the effects of air pollution without grave airway damage.
The MMP-1 molecule is known to enhance the development of certain lung diseases, including COPD. In addition, the tissue-destructive actions of MMP-1 can lead to lung emphysema and the spread of lung cancer.

The study also provides a direction for developing therapeutics for those who are genetically more susceptible to air pollution and airway damage, according to Wolfgang Liedtke, MD, PhD, study author and assistant professor in the Department of Medicine at Duke.

“If we can find a way to stop the hyperactivation of MMP-1 in response to diesel-engine exhaust particles and reduce it to levels that the airways can manage, then we will be helping a large number of people worldwide,” said Liedtke. “It is attractive to envision inhaled TRPV4 inhibitor drugs, rather than swallowing a pill or taking an injection. I envision this as rather similar to inhaled drugs for allergic airway disease that are currently available.”

Source: Duke University Health System