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SCIENTIFIC PUBLICATIONS BY ALR FUNDED RESEARCHERS

Lupus and the Inflammasome

Kaplan, Mariana, MD

University of Michigan

People with lupus develop blood vessel damage that increases their risk of early heart attacks. This blood vessel damage is also thought to contribute to the severity of the kidney disease that occurs later in the disease. Dr. Kaplan’s team has suggested that one mechanism leading to this accelerated blood vessel disease is related to an imbalance between cells that damage and those that repair the lining, or vasculature, of blood vessels. The researchers have previously reported that a molecule called interferon (IFN) alpha plays a crucial role in this process, promoting premature atherosclerosis and kidney damage progression. 

They recently found that IFN-alpha suppresses a molecule called interleukin-1 (IL-1) beta and increases levels of another called IL-18. Both play a role in inflammatory processes. IFN-alpha also activates the machinery that processes these two cytokines, called the inflammasome.

With their grant, Dr. Kaplan and her team will use human and animal systems to better understand how IFN-alpha interacts with the inflammasome machinery, triggering blood vessel damage. They will focus on a specific inflammasome component, caspase-1, exploring how IFN-alpha alters its role to impair blood vessel function and repair.They will also investigate how IFN-alpha reduces production of IL-1 beta and the impact this has on blood vessel function in lupus cells.

What this study means for people with lupus: Identifying the inflammasome as an important mechanism of organ damage and blood vessel abnormalities in SLE could lead to the development of new therapies to prevent the devastating complications of the disease.


1.5 million

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90 million

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