Class IIa Histone Deacetylases Drive Toll-like Receptor-Inducible Glycolysis and Macrophage Inflammatory Responses via Pyruvate Kinase M2

Kaustav Das Gupta; Melanie R. Shakespear; James E.B. Curson; Ambika M.V. Murthy; Abishek Iyer; Mark P. Hodson; Divya Ramnath; Vikas A. Tillu; Jessica B. von Pein; Robert C. Reid; Kathryn Tunny; Daniel M. Hohenhaus; Shayli Varasteh Moradi; Gregory M. Kelly; Takumi Kobayashi; Jennifer H. Gunter; Alexander J. Stevenson; Weijun Xu; Lin Luo; Alun Jones; Wayne A. Johnston; Antje Blumenthal; Kirill Alexandrov; Brett M. Collins; Jennifer L. Stow; David P. Fairlie; Matthew J. Sweet

doi:10.1016/j.celrep.2020.02.007

Class IIa Histone Deacetylases Drive Toll-like Receptor-Inducible Glycolysis and Macrophage Inflammatory Responses via Pyruvate Kinase M2

Kaustav Das Gupta
, Melanie R. Shakespear
, James E.B. Curson
, Ambika M.V. Murthy
, Abishek Iyer
, Mark P. Hodson
, Divya Ramnath
, Vikas A. Tillu
, Jessica B. von Pein
, Robert C. Reid
, Kathryn Tunny
, Daniel M. Hohenhaus
, Shayli Varasteh Moradi
, Gregory M. Kelly
, Takumi Kobayashi
, Jennifer H. Gunter
, Alexander J. Stevenson
, Weijun Xu
, Lin Luo
, Alun Jones

Wayne A. Johnston, Antje Blumenthal, Kirill Alexandrov, Brett M. Collins, Jennifer L. Stow, David P. Fairlie, Matthew J. Sweet^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Research › peer-review

82 Citations (Scopus)

Abstract

Das Gupta et al. show that HDAC7 and other class IIa HDAC enzymes control macrophage metabolism. They initiate TLR-inducible glycolysis in these cells and interact with the glycolytic enzyme PKM2 to drive inflammatory responses in vitro and in vivo. Class IIa HDAC inhibitors may have potential for attenuating immunometabolism-linked inflammation.

Original language	English
Pages (from-to)	2712-2728.e8
Journal	Cell Reports
Volume	30
Issue number	8
DOIs	https://doi.org/10.1016/j.celrep.2020.02.007
Publication status	Published - 25 Feb 2020
Externally published	Yes

Keywords

glycolysis
histone deacetylases
immunometabolism
inflammation
lysine acetylation
macrophage
post-translational modification
pyruvate kinase
toll-like receptor

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10.1016/j.celrep.2020.02.007

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Das Gupta, K., Shakespear, M. R., Curson, J. E. B., Murthy, A. M. V., Iyer, A., Hodson, M. P., Ramnath, D., Tillu, V. A., von Pein, J. B., Reid, R. C., Tunny, K., Hohenhaus, D. M., Moradi, S. V., Kelly, G. M., Kobayashi, T., Gunter, J. H., Stevenson, A. J., Xu, W., Luo, L., ... Sweet, M. J. (2020). Class IIa Histone Deacetylases Drive Toll-like Receptor-Inducible Glycolysis and Macrophage Inflammatory Responses via Pyruvate Kinase M2. Cell Reports, 30(8), 2712-2728.e8. https://doi.org/10.1016/j.celrep.2020.02.007

@article{e13d46cde2c14e8e8663084f18aac19a,

title = "Class IIa Histone Deacetylases Drive Toll-like Receptor-Inducible Glycolysis and Macrophage Inflammatory Responses via Pyruvate Kinase M2",

abstract = "Das Gupta et al. show that HDAC7 and other class IIa HDAC enzymes control macrophage metabolism. They initiate TLR-inducible glycolysis in these cells and interact with the glycolytic enzyme PKM2 to drive inflammatory responses in vitro and in vivo. Class IIa HDAC inhibitors may have potential for attenuating immunometabolism-linked inflammation.",

keywords = "glycolysis, histone deacetylases, immunometabolism, inflammation, lysine acetylation, macrophage, post-translational modification, pyruvate kinase, toll-like receptor",

author = "\{Das Gupta\}, Kaustav and Shakespear, \{Melanie R.\} and Curson, \{James E.B.\} and Murthy, \{Ambika M.V.\} and Abishek Iyer and Hodson, \{Mark P.\} and Divya Ramnath and Tillu, \{Vikas A.\} and \{von Pein\}, \{Jessica B.\} and Reid, \{Robert C.\} and Kathryn Tunny and Hohenhaus, \{Daniel M.\} and Moradi, \{Shayli Varasteh\} and Kelly, \{Gregory M.\} and Takumi Kobayashi and Gunter, \{Jennifer H.\} and Stevenson, \{Alexander J.\} and Weijun Xu and Lin Luo and Alun Jones and Johnston, \{Wayne A.\} and Antje Blumenthal and Kirill Alexandrov and Collins, \{Brett M.\} and Stow, \{Jennifer L.\} and Fairlie, \{David P.\} and Sweet, \{Matthew J.\}",

note = "Publisher Copyright: {\textcopyright} 2020 The Author(s)",

year = "2020",

month = feb,

day = "25",

doi = "10.1016/j.celrep.2020.02.007",

language = "English",

volume = "30",

pages = "2712--2728.e8",

journal = "Cell Reports",

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Das Gupta, K, Shakespear, MR, Curson, JEB, Murthy, AMV, Iyer, A, Hodson, MP, Ramnath, D, Tillu, VA, von Pein, JB, Reid, RC, Tunny, K, Hohenhaus, DM, Moradi, SV, Kelly, GM, Kobayashi, T, Gunter, JH, Stevenson, AJ, Xu, W, Luo, L, Jones, A, Johnston, WA, Blumenthal, A, Alexandrov, K, Collins, BM, Stow, JL, Fairlie, DP & Sweet, MJ 2020, 'Class IIa Histone Deacetylases Drive Toll-like Receptor-Inducible Glycolysis and Macrophage Inflammatory Responses via Pyruvate Kinase M2', Cell Reports, vol. 30, no. 8, pp. 2712-2728.e8. https://doi.org/10.1016/j.celrep.2020.02.007

TY - JOUR

T1 - Class IIa Histone Deacetylases Drive Toll-like Receptor-Inducible Glycolysis and Macrophage Inflammatory Responses via Pyruvate Kinase M2

AU - Das Gupta, Kaustav

AU - Shakespear, Melanie R.

AU - Curson, James E.B.

AU - Murthy, Ambika M.V.

AU - Iyer, Abishek

AU - Hodson, Mark P.

AU - Ramnath, Divya

AU - Tillu, Vikas A.

AU - von Pein, Jessica B.

AU - Reid, Robert C.

AU - Tunny, Kathryn

AU - Hohenhaus, Daniel M.

AU - Moradi, Shayli Varasteh

AU - Kelly, Gregory M.

AU - Kobayashi, Takumi

AU - Gunter, Jennifer H.

AU - Stevenson, Alexander J.

AU - Xu, Weijun

AU - Luo, Lin

AU - Jones, Alun

AU - Johnston, Wayne A.

AU - Blumenthal, Antje

AU - Alexandrov, Kirill

AU - Collins, Brett M.

AU - Stow, Jennifer L.

AU - Fairlie, David P.

AU - Sweet, Matthew J.

PY - 2020/2/25

Y1 - 2020/2/25

N2 - Das Gupta et al. show that HDAC7 and other class IIa HDAC enzymes control macrophage metabolism. They initiate TLR-inducible glycolysis in these cells and interact with the glycolytic enzyme PKM2 to drive inflammatory responses in vitro and in vivo. Class IIa HDAC inhibitors may have potential for attenuating immunometabolism-linked inflammation.

AB - Das Gupta et al. show that HDAC7 and other class IIa HDAC enzymes control macrophage metabolism. They initiate TLR-inducible glycolysis in these cells and interact with the glycolytic enzyme PKM2 to drive inflammatory responses in vitro and in vivo. Class IIa HDAC inhibitors may have potential for attenuating immunometabolism-linked inflammation.

KW - glycolysis

KW - histone deacetylases

KW - immunometabolism

KW - inflammation

KW - lysine acetylation

KW - macrophage

KW - post-translational modification

KW - pyruvate kinase

KW - toll-like receptor

UR - https://www.scopus.com/pages/publications/85079889717

U2 - 10.1016/j.celrep.2020.02.007

DO - 10.1016/j.celrep.2020.02.007

M3 - Article

C2 - 32101747

AN - SCOPUS:85079889717

SN - 2211-1247

VL - 30

SP - 2712-2728.e8

JO - Cell Reports

JF - Cell Reports

IS - 8

ER -

Class IIa Histone Deacetylases Drive Toll-like Receptor-Inducible Glycolysis and Macrophage Inflammatory Responses via Pyruvate Kinase M2

Abstract

Keywords

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