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Updated: Jan 25, 2026

High-throughput Screening for Small-molecule Modulators of Inward Rectifier Potassium Channels
Published on: January 27, 2013
Regulation of interleukin-1 beta secretion from macrophages via modulation of potassium ion (K+ ) channel activity
Jing Wang1, Paul J Yannie2, Siddhartha S Ghosh1
1Department of Internal Medicine, VCU Medical Center, Richmond, VA, USA.
Abstract:
A causal relationship exists between macrophage cholesterol levels and inflammation, for example, Interleukin-1β (IL-1β) secretion. A decrease in intracellular K+ is essential for inflammasome activation/IL-1β secretion and, herein, we examined the hypothesis that cellular cholesterol affects K+ -channel activity and K+ -efflux using mouse peritoneal macrophages (MPMs) and human/THP1 macrophages. An increase in cellular cholesterol led to a significant increase in K+ currents (> 350% in both MPM and THP1). Enhancing cholesterol efflux returned K+ currents back to basal levels with corresponding increase in intracellular K+ (11.2-14.5%) and reduced IL-1β secretion (32-62%). These data demonstrate a novel mechanism by which cellular cholesterol modulates inflammation/inflammasome via regulation of K+ -channel activity and intracellular K+ levels. Attenuation of IL-1β secretion by Nateglinide/Repaglinide further suggests involvement of Kir6 channels.
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