Study summary · research use only
Chemical mitochondrial uncouplers share common inhibitory effect on NLRP3 inflammasome activation through inhibiting NFκB nuclear translocation
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this cell study using RAW264.7 and THP-1-derived macrophages (species not specified beyond these cell lines), the authors characterized the effect of the mitochondrial uncouplers niclosamide, CCCP, and BAM15 on NLRP3 inflammasome activation. They report that all three uncouplers inhibited LPS-plus-ATP-induced increases in NLRP3 protein and IL-1β mRNA levels, and inhibited LPS-plus-ATP-induced NF-κB (P65) phosphorylation and nuclear translocation in RAW264.7 macrophages. Niclosamide and BAM15 inhibited LPS-induced IκBα phosphorylation in RAW264.7 macrophages, an effect the authors describe as dependent on increased intracellular calcium, whereas CCCP showed no significant effect on IκBα phosphorylation. The authors conclude that these chemical mitochondrial uncouplers share a common inhibitory effect on NLRP3 inflammasome activation through inhibiting NF-κB nuclear translocation.
Abstract
Activation of NLRP3 inflammasome is implicated in varieties of pathologies, the aim of the present study is to characterize the effect and mechanism of mitochondrial uncouplers on NLRP3 inflammasome activation by using three types of uncouplers, niclosamide, CCCP and BAM15. Niclosamide, CCCP and BAM15 inhibited LPS plus ATP-induced increases of NLRP3 protein and IL-1β mRNA levels in RAW264.7 macrophages and THP-1 derived macrophages. Niclosamide, CCCP and BAM15 inhibited LPS plus ATP-induced increase of NFκB (P65) phosphorylation, and inhibited NFκB (P65) nuclear translocation in RAW264.7 macrophages. Niclosamide and BAM15 inhibited LPS-induced increase of IκBα phosphorylation in RAW264.7 macrophages, and the inhibitory effect was dependent on increased intracellular [Ca2+]i; however, CCCP showed no significant effect on IκBα phosphorylation in RAW264.7 macrophages stimulated with LPS. In conclusion, chemical mitochondrial uncouplers niclosamide, CCCP and BAM15 share common inhibitory effect on NLRP3 inflammasome activation through inhibiting NFκB nuclear translocation.
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