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

Abstract:

: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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Wang B,Rao YH,Inoue M,Hao R,Lai CH,Chen D,McDonald SL,Choi MC,Wang Q,Shinohara ML,Yao TP

doi

10.1038/ncomms4479

subject

Has Abstract

pub_date

2014-03-17 00:00:00

pages

3479

issn

2041-1723

pii

ncomms4479

journal_volume

5

pub_type

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