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Cigarette Smoke Ups Mucus in Lungs

— Cigarette smoke suppresses a protein whose normal function is to prevent an overpopulation of mucus-producing cells in the lungs, researchers reported.

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Cigarette smoke suppresses a protein whose normal function is to prevent an overpopulation of mucus-producing cells in the lungs, researchers reported.

Suppression of the so-called Bik protein leads to hyperplasia of airway epithelial cells and mucous cell metaplasia, according to Yohannes Tesfaigzi, PhD, of the Lovelace Respiratory Research Institute in Albuquerque, N.M., and colleagues.

The finding could lead to treatments for chronic bronchitis, Tesfaigzi and colleagues reported online in the American Journal of Respiratory and Critical Care Medicine.

Action Points

  • Explain that cigarette smoke suppresses a protein whose normal function is to prevent an overpopulation of mucus-producing cells in the lung.
  • Note that levels of the protein, Bik, were significantly reduced in the airway tissue of former smokers with chronic bronchitis, and that restoration of Bik expression is a potential therapeutic target for future research.

Over-secretion of mucus is a characteristic of chronic bronchitis, which affects many cigarette smokers and is associated with chronic obstructive pulmonary disease, Tesfaigzi and colleagues noted.

Normally, mucus secretion increases in the airway epithelium in response to bacteria or viral infectious agents and environmental pollutants. An inflammatory response kickstarts the proliferation of epithelial cells that produce the protective substance.

In previous research, Tesfaigzi and colleagues noted that they had found a 30% drop in the number of such cells after the end of the inflammatory response, a decline driven by apoptosis regulated by the Bcl-2 family of proteins.

In mice, the proteins involved are STAT1 and Bik, and the researchers thought the same might hold true in humans. To test the hypothesis, they looked first at cells obtained by bronchial brushing from 20 volunteers, including 11 with chronic bronchitis and nine with no lung disease.

For the analysis, chronic bronchitis was defined as a daily cough with phlegm production for three consecutive months, two years in a row.

Analysis of the brushings by polymerase chain reaction showed that Bik -- but not a range of the other Bcl-2 proteins -- was reduced significantly (P<0.05) in the cells from those with bronchitis, compared with those with no lung disease, the researchers reported.

To confirm the analysis, they looked at airway tissue obtained on autopsy from four people who were smokers when they died, six former smokers who had reported chronic bronchitis, six former smokers who had not had chronic bronchitis, and five people who had never smoked.

Levels of Bik were significantly reduced (P<0.05) in the airway tissue of the former smokers with bronchitis, compared with those former smokers who did not have the condition, they found.

In an animal experiment, mice were exposed to cigarette smoke or filtered air for 10 weeks. The researchers found that Bik levels dropped by 50% in those exposed to the smoke, and levels of Muc5ac -- a protein that is a major component of mucus -- increased by a factor of three, compared with controls.

A subsequent experiment showed that both changes were sustained even if the mice were exposed to cigarette smoke for three weeks and then allowed to recover for 60 days breathing filtered air, they reported.

Finally, Tesfaigzi and colleagues exposed mice to cigarette smoke for three weeks and then transfected them with a vector containing the Bik gene. Epithelial cell hyperplasia was significantly reduced within a day (P<0.05) compared with animals given a control vector.

"These studies lay the foundation to investigate therapies that may restore expression of Bik and reduce the numbers of mucus-producing cells," Tesfaigzi said in a statement. "This method may reduce excess secretion of mucus and the airway blockages in patients with chronic bronchitis."

Disclosures

The study was supported by the NIH and the Flight Attendant Medical Research Institute. The authors did not report any conflicts.

Primary Source

American Journal of Respiratory and Critical Care Medicine

Mebratu YA, et al "Cigarette smoke suppresses Bik to cause epithelial cell hyperplasia and mucous cell metaplasia" Am J Respir Crit Care Med 2011; DOI:10.1164/rccm.201011-1930OC.