ACLY inhibitor reduced Porphyromonas gingivalis-induced pyroptosis by suppressing microtubules acetylation in macrophages.

OBJECTIVES

This study aimed to investigate the effect of acetylation of α-tubulin induced by ATP-citrate lyase (ACLY) activation on pyroptosis process in mouse bone marrow derived macrophages (BMDMs).

MATERIALS AND

METHODS

Level of phospho-ACLY was assessed in normal and inflamed gingiva. Mouse BMDMs were harvested and infected with Porphyromonas gingivalis. The mRNA and protein levels of genes were analyzed by real-time quantitative PCR and western blotting, respectively. Polymerization and acetylation of microtubules were detected with immunofluorescence. Lactate dehydrogenase (LDH) activity assay, immunofluorescence, and ELISA were performed to determine pyroptosis in P.gingivalis-induced BMDMs.

RESULTS

Elevated expression of phospho-ACLY was observed in the inflamed gingiva. P. gingivalis infection was shown to promote pyroptosis in mouse BMDMs. Moreover, P. gingivalis-induced BMDMs showed increased phospho-ACLY, as well as polymerization and acetylation of microtubules. Inhibition and knockdown of ACLY showed depolymerization and decreased acetylation of microtubules, thus resulting in reduced P. gingivalis-induced pyroptosis in BMDMs.

CONCLUSIONS

Our findings suggest that ACLY-mediated dynamics of microtubules participate in the progress of periodontitis. P. gingvalis-triggered phospho-ACLY target the microtubule cytoskeleton by influencing acetylation of tubulin, facilitating NLRP3 inflammasome activation and pyroptosis.