While inflammation usually protects the body from injury, infection and toxins, sometimes the immune system response goes too far and itself causes harm. A new Northwestern Medicine study shows that a protein called vimentin may help activate an inflammatory response that leads to acute lung injury.
The paper demonstrates that vimentin acts as a key regulator for a set of protein interactions that can cause inflammation and thick, stiff scarring in the lungs called pulmonary fibrosis, which makes it difficult for patients to breathe.
"This study advances our understanding of vimentin and the role that it plays in orchestrating early inflammatory responses of the innate immune system," said senior author Dr Karen Ridge associate professor in medicine-pulmonary and cell and molecular biology. Specifically, Ridge and colleagues showed that vimentin acts as a scaffold in cells where a multi-protein complex called the NLRP3 inflammasome can assemble. There, the complex activates caspase-1 and then IL-1β, the protein that ultimately induces the injuries to the lungs.
"We think vimentin is a platform that's required for this assembly and activation of the NLRP3 inflammasome," Ridge said. "This is important because we haven't been able to target caspase-1 or IL-1β very effectively. But vimentin is a very stable protein that we can hopefully target by developing a drug to disrupt its function."
The scientists tested three different mouse models of lung injury in the study and found that vimentin deficiency consistently reduced the inflammatory response that leads to lung injury and pulmonary fibrosis. Ridge’s lab prevented the production of vimentin in mouse models genetically; in future research, they hope to develop tools to do so pharmacologically. The group is also investigating how the same protein is involved in the stabilisation of the NLRP3 inflammasome in response to influenza.
[link url="http://www.feinberg.northwestern.edu/news/2015/04/Ridge-vimentin-lung-injury.html"]Northwestern Medicine material[/link]
[link url="http://www.nature.com/ncomms/2015/150312/ncomms7574/full/ncomms7574.html"]Nature Communications abstract[/link]