PMID- 24480366
OWN - NLM
STAT- MEDLINE
DCOM- 20141209
LR  - 20181202
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 265
DP  - 2014 Apr 18
TI  - Histone deacetylase inhibitors valproic acid and sodium butyrate enhance 
      prostaglandins release in lipopolysaccharide-activated primary microglia.
PG  - 147-57
LID - S0306-4522(14)00057-8 [pii]
LID - 10.1016/j.neuroscience.2014.01.037 [doi]
AB  - Modifications of histone deacetylases (HDACs) may be involved in microglia-driven 
      neuroinflammatory responses. Recent studies suggest that several inflammatory 
      molecules can regulate the extent of neurodegeneration and regeneration in the 
      central nervous system (CNS). In the present study, we investigated the effects 
      of HDAC inhibitors (HDACi) valproic acid (VPA) and sodium butyrate (NaBut) on the 
      release of prostaglandins (PGs) in lipopolysaccharide (LPS)-activated microglia. 
      We found that VPA and NaBut significantly enhanced LPS-induced release of PGE2, 
      PGD2 and 8-iso-PGF2alpha. In addition, both compounds increased cyclooxygenase-2 and 
      microsomal prostaglandin E synthase immunoreactivity and gene expression in 
      LPS-stimulated microglia. Interestingly, treatment of activated microglia with 
      HDACi also enhanced the gene expression and the release of different 
      pro-inflammatory cytokines. Microglia activation with LPS leads to IkappaB-alpha 
      degradation, as well as p38, ERK1/2 and JNK MAPKs phosphorylation and thus 
      activation, which is not affected by treatment with VPA and NaBut. Furthermore, 
      VPA and NaBut treatment induced histone acetylation at H3-K18 in microglia. We 
      suggest that VPA and NaBut-driven increase in PGs release in LPS-activated 
      microglia might be regulated at the transcriptional level and involves histone 
      hyperacetylation. Our data demonstrate that VPA and NaBut are able to modulate 
      microglia responses to inflammatory insults and thus possibly can regulate the 
      CNS degenerative and regenerative processes.
CI  - Copyright (c) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Singh, V
AU  - Singh V
AD  - Department of Psychiatry, University of Freiburg Medical School, Hauptstrasse 5, 
      D-79104 Freiburg, Germany.
FAU - Bhatia, H S
AU  - Bhatia HS
AD  - Department of Psychiatry, University of Freiburg Medical School, Hauptstrasse 5, 
      D-79104 Freiburg, Germany. Electronic address: 
      harsharan.singh.bhatia@uniklinik-freiburg.de.
FAU - Kumar, A
AU  - Kumar A
AD  - Department of Psychiatry, University of Freiburg Medical School, Hauptstrasse 5, 
      D-79104 Freiburg, Germany; University of Freiburg, Faculty of Biology, 
      Schaenzlestrasse 1, D-79104 Freiburg, Germany.
FAU - de Oliveira, A C P
AU  - de Oliveira AC
AD  - Department of Psychiatry, University of Freiburg Medical School, Hauptstrasse 5, 
      D-79104 Freiburg, Germany; Department of Pharmacology, Universidade Federal de 
      Minas Gerais, Avenida Antonio Carlos 6627, 31270-901 Belo Horizonte, Minas 
      Gerais, Brazil.
FAU - Fiebich, B L
AU  - Fiebich BL
AD  - Department of Psychiatry, University of Freiburg Medical School, Hauptstrasse 5, 
      D-79104 Freiburg, Germany; VivaCell Biotechnology GmbH, Ferdinand-Porsche-Strasse 
      5, D-79211 Denzlingen, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140128
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Prostaglandins)
RN  - 107-92-6 (Butyric Acid)
RN  - 614OI1Z5WI (Valproic Acid)
SB  - IM
MH  - Animals
MH  - Butyric Acid/*pharmacology
MH  - Cells, Cultured
MH  - Histone Deacetylase Inhibitors/*pharmacology
MH  - Lipopolysaccharides/pharmacology
MH  - Microglia/*drug effects/*metabolism
MH  - Prostaglandins/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Valproic Acid/*pharmacology
OTO - NOTNLM
OT  - cyclooxygenase-2
OT  - histone deacetylase inhibitors
OT  - microglia
OT  - microsomal prostaglandin E synthase-1
OT  - prostaglandin
EDAT- 2014/02/01 06:00
MHDA- 2014/12/15 06:00
CRDT- 2014/02/01 06:00
PHST- 2013/09/10 00:00 [received]
PHST- 2014/01/17 00:00 [revised]
PHST- 2014/01/19 00:00 [accepted]
PHST- 2014/02/01 06:00 [entrez]
PHST- 2014/02/01 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
AID - S0306-4522(14)00057-8 [pii]
AID - 10.1016/j.neuroscience.2014.01.037 [doi]
PST - ppublish
SO  - Neuroscience. 2014 Apr 18;265:147-57. doi: 10.1016/j.neuroscience.2014.01.037. 
      Epub 2014 Jan 28.