Pollutants cause breathing problems by disrupting cell development

Chemicals found in car exhaust fumes and cigarette smoke disrupt genetic factors that make cilia - the brush-like structures on cells that sweep mucus, dirt and bacteria out of the lung - researchers at the Francis Crick Institute in London have discovered.

Breathing in air pollution creates a 'molecular distraction' that changes cell behaviour so much it could cause respiratory disease, they suggest.

The collaboration between Dr Brigitta Stockinger and Dr Andreas Wack, published today (Wed 24 Aug 2016) in the journal Nature Communications, reveals the role of a protein called aryl hydrocarbon receptor (AhR) in keeping airways healthy. AhR is active in cells that line the human airway and lungs and is crucial for cilia formation. They've found in animal studies that air pollutants make it harder for AhR to fulfil its role in formation of new cilia.

The research provides the first evidence of a link between air pollution, AhR and respiratory disease. The team was funded by the Medical Research Council and Wellcome.

"We think AhR may be the molecular link between air pollution and chronic respiratory disease, especially in childhood conditions triggered by pollution. Our research shows that chemicals commonly found in air pollution interfere with formation of tiny hair like structures called cilia by changing AhR's behaviour," says Dr Wack of the Francis Crick Institute. 

Dr Stockinger, another group leader at the Crick, explains: "When chemicals found in car exhaust fumes and cigarette smoke activate AhR it kick starts a chain reaction that diverts attention away from forming new cilia. Instead AhR tries to start a detox programme."

The team grew airway cells from mice and skin cells from frogs in the lab to study how AhR works and what impact pollutants have. Both frog skin and mouse airway cells have many cilia that move mucus about in the same way cilia do in cells in the human throat and lungs.

They found that when these animal cells are exposed to common pollutants fewer cilia are formed because the AhR responds to pollutants by trying to detox the environment rather than by making new cilia. It has long been established that if a person is missing cilia they will experience respiratory disease. Stockinger and Wack's new study details the molecular and genetic mechanisms that link pollutants to fewer cilia, and so to breathing problems.

Dr Wack said: "We've established a clear link between environmental pollutants and reduced ability to grow new cilia. Essentially pollutants change the way the body behaves at a molecular level, divert attention and push a detox rather than new cilia growth programme. Fewer cilia means less mucus clear-out and a higher risk of the infections and breathing problems that are features of respiratory disease."

The aryl hydrocarbon receptor controls cyclin O to promote epithelial multiciliogenesis is published in Nature Communications. 


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