epothilone-a and Bacterial-Infections

Microtubules play critical roles in regulating the activation of NLRP3 inflammasome and microtubule-destabilizing agents such as colchicine have been shown to suppress the activation of this inflammasome. However, it remains largely unknown whether paclitaxel, a microtubule-stabilizing agent being used in cancer therapy, has any influences on NLRP3 inflammasome activation. Here we showed that paclitaxel pre-treatment greatly enhanced ATP- or nigericin-induced NLRP3 inflammasome activation as indicated by increased release of cleaved caspase-1 and mature IL-1β, enhanced formation of ASC speck, and increased gasdermin D cleavage and pyroptosis. Paclitaxel time- and dose-dependently induced α-tubulin acetylation in LPS-primed murine and human macrophages and further increased ATP- or nigericin-induced α-tubulin acetylation. Such increased α-tubulin acetylation was significantly suppressed either by resveratrol or NAD

Topics: Acetylation; Acetyltransferases; Animals; Bacterial Infections; Cell Line; Disease Models, Animal; Epothilones; Gene Knockdown Techniques; Humans; Immunity, Innate; Inflammasomes; Interleukin-1beta; Macrophages; Mice; Microtubule Proteins; Microtubules; Nigericin; NLR Family, Pyrin Domain-Containing 3 Protein; Paclitaxel; Pyroptosis; Signal Transduction; THP-1 Cells; Tubulin