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Protein speck pinpointed in respiratory disease inflammation

Jul 1 2014

Professor Phil Hansbro

Sinister specks of a molecule known as ASC are escaping from cells then coursing through the body to exacerbate the biological inflammatory response in major airway diseases such as asthma and emphysema.

That is the ground-breaking discovery, just published in the international journal Nature Immunology, resulting from a collaboration between University of Newcastle respiratory researchers Professor Phil Hansbro, Bernadette Jones and Dr Andrew Jarnicki along with a team from the University of Bonn in Germany.

In shedding new light on an immunological factor known as the inflammasome, it potentially takes researchers closer to being able to inhibit inflammatory conditions at their genesis.

“Inflammasomes are a recently discovered complex of proteins that form once a cell is exposed to a pathogen such as a virus or bacterial infection. They trigger the release of a load of inflammatory proteins,” Professor Hansbro said. “They are normally beneficial in response to infection but can become abnormally activated and may lead to chronic respiratory diseases.

“Previously it was thought that an inflammasome was confined to a single cell and that each cell needed to be activated independently [by the pathogen] but this study shows for the first time that there is a broader release of the ASC protein.

“The ASC specks escape, they travel around the body and induce inflammasomes in the new host cells. In other words, it takes just a few cells for ASC specks to activate lots of other cells.”

Professor Hansbro says the process occurs during the body’s initial “non-specific” immune response to pathogenic challenges, often preventing further infection by destroying the bacteria and viruses before they reproduce. However the specks retain their ability to trigger inflammation even after the demise of the original cell.

“Humans suffer a lot of inflammatory diseases – asthma, emphysema, arthritis, pneumonia and so on – and we’re now thinking that we may have an overactive baseline inflammatory response,” Professor Hansbro added. “Because it’s active all the time, it drives this continual cycle of inflammation … it becomes exaggerated and uncontrollable, which could underpin why we get asthma attacks or COPD exacerbations for example.

“If we can develop inhibitors to this process we might be able to restore the perpetual inflammatory response to normal. People can still respond to infections but won’t develop an inflammatory disease.”

The finding is set to spur the development of drugs that will either target the ASC specks themselves or the initial inflammasome source.

* Professor Phil Hansbro is chair of Microbiology in the School of Biomedical Sciences & Pharmacy at the University of Newcastle, Associate Director of the Priority Research Centre for Asthma and Respiratory Disease, and Leader of the Asthma and Airways Research Group in HMRI’s VIVA Program. HMRI is a partnership between the University of Newcastle, Hunter New England Health and the community.