biostudies-literatureWang JBLRD VANCI NIH HHSU.S. Department of Veterans Affairs1166-1178https://www.ebi.ac.uk/biostudies/studies/S-EPMC6557664biostudies-literatureUnknown593(11)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 ceFEBS lettersRegulation of interleukin-1 beta secretion from macrophages via modulation of potassium ion (K⁺ ) channel activity.PMC6557664I01 BX002297P30 CA016059Ghosh SYannie PJGhosh SSWang JfalseRegulation of interleukin-1 beta secretion from macrophages via modulation of potassium ion (K⁺ ) channel activity.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 ce2019-01-01T00:00:00Z2019 Jun2025-04-19T14:24:33.42Z2020-10-29T16:40:21ZS-EPMC65576643102635710.1002/1873-3468.13395