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Regulation of interleukin‐1 beta secretion from macrophages via modulation of potassium ion (K + ) channel activity
Author(s) -
Wang Jing,
Yannie Paul J.,
Ghosh Siddhartha S.,
Ghosh Shobha
Publication year - 2019
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13395
Subject(s) - secretion , intracellular , inflammasome , potassium channel , endocrinology , inflammation , medicine , chemistry , efflux , microbiology and biotechnology , biology , biochemistry
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/ THP 1 macrophages. An increase in cellular cholesterol led to a significant increase in K + currents (> 350% in both MPM and THP 1). 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.