Microtubule acetylation amplifies p38 kinase signalling and anti-inflammatory IL-10 production.

Journal Article (Journal Article)

Reversible acetylation of α-tubulin is an evolutionarily conserved modification in microtubule networks. Despite its prevalence, the physiological function and regulation of microtubule acetylation remain poorly understood. Here we report that macrophages challenged by bacterial lipopolysaccharides (LPS) undergo extensive microtubule acetylation. Suppression of LPS-induced microtubule acetylation by inactivating the tubulin acetyltransferase, MEC17, profoundly inhibits the induction of anti-inflammatory interleukin-10 (IL-10), a phenotype effectively reversed by an acetylation-mimicking α-tubulin mutant. Conversely, elevating microtubule acetylation by inhibiting the tubulin deacetylase, HDAC6, or stabilizing microtubules via Taxol stimulates IL-10 hyper-induction. Supporting the anti-inflammatory function of microtubule acetylation, HDAC6 inhibition significantly protects mice from LPS toxicity. In HDAC6-deficient macrophages challenged by LPS, p38 kinase signalling becomes selectively amplified, leading to SP1-dependent IL-10 transcription. Remarkably, the augmented p38 signalling is suppressed by MEC17 inactivation. Our findings identify reversible microtubule acetylation as a kinase signalling modulator and a key component in the inflammatory response.

Full Text

Duke Authors

Cited Authors

  • Wang, B; Rao, Y-H; Inoue, M; Hao, R; Lai, C-H; Chen, D; McDonald, SL; Choi, M-C; Wang, Q; Shinohara, ML; Yao, T-P

Published Date

  • March 17, 2014

Published In

Volume / Issue

  • 5 /

Start / End Page

  • 3479 -

PubMed ID

  • 24632940

Pubmed Central ID

  • PMC4000527

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/ncomms4479


  • eng

Conference Location

  • England