Last updated February 22, 2018 at 9:37 am
Scientists have discovered the mechanism that turns on and off inflammation, with implications for treating chronic diseases such as Alzheimer’s and gout.
Inflammation is a double-edged sword in the progress of many illnesses. At the onset of a disease, an inflammatory response by the body’s immune system is essential to ensure optimal pathogen-fighting as well as to protect the integrity of the central nervous system (CNS).
However, in many diseases, such as Alzheimer’s or gout, the inflammation process continues well beyond this initial phase and ends up causing much more harm than good.
Long-term inflammation contributes to the chronic progression of such diseases, in what has been termed “a vicious self-propagating cycle”.
So far, the mechanism that causes – or fails to stop – uncontrolled inflammation has remained unclear. But researchers from the University of Queensland’s Institute for Molecular Biosciences (IMB) report a major step forward in solving the mystery.
In a paper published in the Journal of Experimental Medicine, a team led by the IMB’s Associate Professor Kate Schroder, reveal the mechanism by which the inflammation process cuts off in healthy cells – opening the way to possibly controlling it during illness.
Inflammation implicated in chronic diseases
Schroder and her team focussed on the role of chemical complexes known as inflammasomes – receptors and sensors within cells that regulate an enzyme called caspase-1, which triggers inflammation.
Inflammasome function, or dysfunction, is strongly implicated in the progression of many chronic diseases, but its precise role has eluded discovery.
“These complexes form when an infection, injury or other disturbance is detected by the immune system, and they send messages to immune cells to tell them to respond,” says Schroder.
“If the disturbance can’t be cleared, such as in the case of amyloid plaques in Alzheimer’s, these molecular machines continue to fire, resulting in neurodegenerative damage from the sustained inflammation.”
The team at the IMB’s Centre for Inflammation and Disease Research established that inflammasome activates caspase-1, which initiates an inflammation response by snipping away a part of its own structure.
‘Off switch’ for inflammatory response
In healthy cells, an inbuilt timing mechanism then comes into play after a certain period, with the inflammasome inducing the caspase-1 to cut itself again and thus halt its activity.
Discovering this mechanism offers a “molecular basis” to cause signal shutdown in cases where inflammation has become ongoing, the scientists report.
Schroder’s team is looking specifically at a condition in which chronic inflammation is a major obstacle to treatment: fatty liver disease.
“In some patients with this condition the liver becomes increasingly fatty and inflamed, and this can lead to cirrhosis – which can require liver transplantation – or even liver cancer,” she said.
IMB researchers have already developed compounds that block inflammasome function, and have created a start-up company, Inflazome Ltd, to bring them to market.