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.