August 29, 2018
Blood vessels are prone to inflame
The immune system serves to combat almost any illness or infection. While its intention is to cure, the immune system can also cause discomfort through inflammation. Indeed, many diseases are accompanied or even caused by chronic inflammation. A new study by Associate Professor Megumu Saito and his laboratory provides a new explanation for the common inflammation seen in vascular diseases like atherosclerosis.
"The inflammasome is one of the most critical machineries for regulating the innate immune response," says Saito. "It operates through two sequential signals, a priming signal and an activating signal."
The inflammasome can be further subcategorized. NLRP3 inflammasome is a popular focus of researchers, because of its role in various inflammatory disorders. NLRP3 inflammasome controls the expression of interleukin-1β (IL-1β), which is one of the oldest known and most studied of inflammatory molecules, or cytokines.
Although the inflammasome is generally believed to require two signals, there are known exceptions.
"One signal is enough to produce IL-1β from monocytes," which are a type of white blood cell, explains Saito.
Vascular smooth muscles make up the walls of almost all blood vessels and are responsible for controlling the diameter of the vessels. Unexpected observations in preliminary experiments led Saito to wonder if these cells can also activate NLRP3 inflammasome with just one signal like monocytes.
To test this theory, the scientists primed vascular smooth cells and monocytes with the destruction of lysozymes, a type of enzyme found inside cells and whose loss stimulates inflammation but also cell death.
Interestingly, the destruction of lysozymes caused monocytes to die, but vascular smooth cells survived to secrete IL-1β.
"Our results show that one signal is enough to both prime and activate the inflammasome in vascular smooth cells. We don't know the reason why the cells responded differently," says Saito.
Saito adds that the findings suggest a unique signal could trigger inflammation in blood vessels.
"Classically, the vasculature does not inflame until it is invaded by immune cells. Our findings suggest the inflammation can occur before the invasion," he says.
- Journal: Inflammation Research
- Title: Lysosomal membrane permeabilization causes secretion of IL-1β in human vascular smooth muscle cells
- Authors: Hiroaki Ono1,2, Hidetoshi Takada2, Akira Niwa1, Tatsutoshi Nakahata1, Shouichi Ohga2, and Megumu K. Saito1
- Author Affiliations:
- Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan
- Department of Pediatrics, Faculty of Medical Science, Kyushu University, Fukuoka, Japan