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Guo-Ping Shi

Guo-Ping Shi, DSc., a biochemist in BWH’s Cardiovascular Division, and his team have explored whether the absence of the receptor for interleukin 18 (IL18), an inflammatory cell signaling protein, affects the hardening of the arteries. The team has also uncovered surprising evidence about IL18’s interactions. The research team’s findings appear in Nature Medicine.

The cell signaling protein, or cytokine, IL18 plays a well-known role in many inflammatory diseases including atherosclerosis, the buildup of plaque on the inner side of artery walls. The condition is serious as it could lead to heart attack, stroke and death.

Previous pre-clinical studies have indicated that IL18 deficiency can block atherosclerosis progression. However, Shi’s team found a genetic deficiency of the conventional IL18 receptors did not have any influence on atherosclerosis. The team hypothesized that another molecule may be involved, and went on to discover that IL18 uses a sodium-chloride co-transporter to mediate the inflammatory function of atherosclerosis.

Through this work, the team demonstrated that IL18 receptors are not the sole receptors in modulating IL18 actions in atherosclerosis. They also discovered Na-Cl co-transporters, ion channel proteins that are normally expressed in the kidney and control the flow of ions like sodium and chlorine into or out of a cell, have another function as an IL18 receptor.

According to Shi, this is the first evidence that ion channel proteins act as receptors for cytokines.

Expression of Na-Cl co-transporters and conventional IL18 receptors in macrophages, endothelial cells, and smooth muscle cells from atherosclerotic lesions.

Expression of Na-Cl co-transporters and conventional IL18 receptors in macrophages, endothelial cells, and smooth muscle cells from atherosclerotic lesions.