PMID- 32849638
OWN - NLM
STAT- MEDLINE
DCOM- 20210412
LR  - 20211204
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 11
DP  - 2020
TI  - HDAC6 Mediates Poly (I:C)-Induced TBK1 and Akt Phosphorylation in Macrophages.
PG  - 1776
LID - 10.3389/fimmu.2020.01776 [doi]
LID - 1776
AB  - Macrophages are derived from monocytes in the bone marrow and play an important 
      role in anti-viral innate immune responses. Macrophages produce cytokines such as 
      interferons and IL-10 upon viral infection to modulate anti-viral immune 
      responses. Type I interferons (IFNs) promote anti-viral defense. IL-10 is a 
      suppressor cytokine that down-regulates anti-viral immune responses. HDAC6 is a 
      tubulin deacetylase that can modulate microtubule dynamics and 
      microtubule-mediated cell signaling pathways. In the present study, we 
      investigated the potential role of HDAC6 in macrophage anti-viral responses by 
      examining poly (I:C)-induced IFN-beta and IL-10 production in mouse bone 
      marrow-derived macrophages (BMDMs). We also investigated the role of HDAC6 in 
      poly (I:C)-induced anti-viral signaling such as TBK1, GSK-3beta, and Akt activation 
      in mouse BMDMs. Our data showed that HDAC6 deletion enhanced poly (I:C)-induced 
      INF-beta expression in macrophages by up-regulating TBK1 activity and eliminating 
      the inhibitory regulation of GSK-3beta. Furthermore, HDAC6 deletion inhibited poly 
      (I:C)-induced suppressor cytokine IL-10 production in the BMDMs, which was 
      associated with the inhibition of Akt activation. Our results suggest that HDAC6 
      modulates IFN-beta and IL-10 production in macrophages through its regulation of 
      TBK1, GSK-3beta, and Akt signaling. HDAC6 could act as a suppressor of anti-viral 
      innate immune responses in macrophages.
CI  - Copyright (c) 2020 Wang, Wang and Fu.
FAU - Wang, Yan
AU  - Wang Y
AD  - Department of Respiratory and Critical Care Medicine, The Second Hospital of 
      Jilin University, Changchun, China.
AD  - Department of Toxicology and Cancer Biology, College of Medicine, University of 
      Kentucky, Lexington, KY, United States.
FAU - Wang, Ke
AU  - Wang K
AD  - Department of Respiratory and Critical Care Medicine, The Second Hospital of 
      Jilin University, Changchun, China.
FAU - Fu, Jian
AU  - Fu J
AD  - Department of Toxicology and Cancer Biology, College of Medicine, University of 
      Kentucky, Lexington, KY, United States.
LA  - eng
PT  - Journal Article
DEP - 20200811
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - EC 2.7.1.- (Tbk1 protein, mouse)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.5.1.98 (Hdac6 protein, mouse)
RN  - EC 3.5.1.98 (Histone Deacetylase 6)
RN  - O84C90HH2L (Poly I-C)
SB  - IM
MH  - Animals
MH  - Gene Expression Regulation/*immunology
MH  - Histone Deacetylase 6/*immunology
MH  - Immunity, Innate/immunology
MH  - Macrophages/*immunology/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Phosphorylation
MH  - Poly I-C/immunology/pharmacology
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Virus Diseases/immunology
PMC - PMC7431618
OTO - NOTNLM
OT  - acetylation
OT  - cytokine
OT  - infection
OT  - innate immunity
OT  - microtubule
EDAT- 2020/08/28 06:00
MHDA- 2021/04/13 06:00
PMCR- 2020/01/01
CRDT- 2020/08/28 06:00
PHST- 2020/05/24 00:00 [received]
PHST- 2020/07/03 00:00 [accepted]
PHST- 2020/08/28 06:00 [entrez]
PHST- 2020/08/28 06:00 [pubmed]
PHST- 2021/04/13 06:00 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2020.01776 [doi]
PST - epublish
SO  - Front Immunol. 2020 Aug 11;11:1776. doi: 10.3389/fimmu.2020.01776. eCollection 
      2020.