HOUSE DUST MITES CAUSE DNA DAMAGE AND CELL DEATH IN LUNG, WORSENING ASTHMA

Asthma affects 300 million people globally, with 250,000 people dying from it every year. The house dust mite (HDM) is a major cause of allergic asthma, with approximately 50% to 80% of asthmatic patients found to be allergic to HDM. Approximately 0.3 mm in size, as many as 2 million dust mites can infest an average-sized mattress.

The allergic response to HDM has been well characterised. However, another damaging effect of HDM has now been reported by researchers at the Department of Pharmacology of NUS Medicine and the Singapore-MIT Alliance for Research and Technology (SMART). The researchers found that HDM directly causes DNA damage and cell death in lung epithelial cells, the cells lining the airways in the lung. The work was published online on May 2 in the Journal of Allergy and Clinical Immunology, the most cited journal in its field.

Reactive oxygen and nitrogen species (RONS) released by activated immune cells are potent inducers of DNA damage. SMART PhD student Tze Khee Chan, along with her advisors Associate Professor W.S. Fred Wong of Department of Pharmacology, NUS and Professor Bevin Engelward of Massachusetts Institute of Technology (MIT) and

other colleagues, discovered that the lung epithelial cells themselves produce RONS in response to HDM. The RONS can potentially damage the DNA of the lung epithelial cells. If the damaged DNA is not adequately repaired, it could lead to cell death and promote inflammation that worsens asthma.

In response to DNA damage, the cell’s DNA repair machinery kicks into gear. This is the system that is constantly fixing errors in the DNA that occur because of environmental assaults or as a by-product of cell division. The authors found that blocking DNA repair resulted in more DNA damage and cell death in both cultured lung epithelial cells and an experimental mouse asthma model. Thus, a person’s DNA repair capability could help to determine how susceptible that person is to developing chronic asthma. These findings provide new insights into the processes underlying allergic asthma and suggest new ways to predict susceptibility for the disease.


FACT BOX

DNA Repair and Asthma:

  • In asthma, DNA damage in lung epithelial cells activates the DNA repair process
  • DNA repair may help to keep airways in the lung functioning properly
  • Blocking DNA repair causes more DNA damage and cell death

An individual’s DNA repair capacity could help to determine how susceptible he or she is to developing asthma