PMID- 29226424
OWN - NLM
STAT- MEDLINE
DCOM- 20180830
LR  - 20180830
IS  - 1098-1136 (Electronic)
IS  - 0894-1491 (Linking)
VI  - 66
IP  - 4
DP  - 2018 Apr
TI  - Activation of EP(2) receptor suppresses poly(I: C) and LPS-mediated inflammation 
      in primary microglia and organotypic hippocampal slice cultures: Contributing 
      role for MAPKs.
PG  - 708-724
LID - 10.1002/glia.23276 [doi]
AB  - Brain inflammation is a critical factor involved in neurodegeneration. Recently, 
      the prostaglandin E(2) (PGE(2) ) downstream members were suggested to modulate 
      neuroinflammatory responses accompanying neurodegenerative diseases. In this 
      study, we investigated the protective effects of prostaglandin E(2) receptor 2 
      (EP(2) ) during TLR3 and TLR4-driven inflammatory response using in vitro primary 
      microglia and ex vivo organotypic hippocampal slice cultures (OHSCs). Depletion 
      of microglia from OHSCs differentially affected TLR3 and TLR4 receptor 
      expression. Poly(I:C) induced the production of prostaglandin E(2) in OHSCs by 
      increasing cyclooxygenase (COX-2) and microsomal prostaglandin E synthase 
      (mPGES)-1. Besides, stimulation of OHSCs and microglia with Poly(I:C) upregulated 
      EP(2) receptor expression. Co-stimulation of OHSCs and microglia with the EP(2) 
      agonist butaprost reduced inflammatory mediators induced by LPS and Poly(I:C). In 
      Poly(I:C) challenged OHSCs, butaprost almost restored microglia ramified 
      morphology and reduced Iba1 immunoreactivity. Importantly, microglia depletion 
      prevented the induction of inflammatory mediators following Poly(I:C) or LPS 
      challenge in OHSCs. Activation of EP(2) receptor reversed the 
      Poly(I:C)/LPS-induced phosphorylation of the mitogen activated protein kinases 
      (MAPKs) ERK, p38 MAPK and c-Jun N-terminal kinase (JNK) in microglia. 
      Collectively, these data identify an anti-inflammatory function for EP(2) 
      signaling in diverse innate immune responses, through a mechanism that involves 
      the mitogen-activated protein kinases pathway.
CI  - (c) 2017 Wiley Periodicals, Inc.
FAU - Yousif, Nizar M
AU  - Yousif NM
AUID- ORCID: 0000-0003-2501-9173
AD  - Neurochemistry Research Group, Department of Psychiatry and Psychotherapy, 
      Medical Center - University of Freiburg, Faculty of Medicine, University of 
      Freiburg, Hauptstr. 5, Freiburg, D-79104, Germany.
AD  - Faculty of Biology, University of Freiburg, Freiburg, Germany.
FAU - de Oliveira, Antonio Carlos Pinheiro
AU  - de Oliveira ACP
AD  - Department of Pharmacology, Universidade Federal de Minas Gerais, Av. Antonio 
      Carlos 6627, Belo Horizonte, 31270-901, Brazil.
FAU - Brioschi, Simone
AU  - Brioschi S
AD  - Faculty of Biology, University of Freiburg, Freiburg, Germany.
AD  - Department of Psychiatry and Psychotherapy, Medical Center - University of 
      Freiburg, Faculty of Medicine, University of Freiburg, Hauptstr. 5, Freiburg, 
      D-79104, Germany.
FAU - Huell, Michael
AU  - Huell M
AD  - Zentrum fur Psychiatrie Emmendingen, Neubronnstr. 25, Emmendingen, 79312.
FAU - Biber, Knut
AU  - Biber K
AD  - Department of Psychiatry and Psychotherapy, Medical Center - University of 
      Freiburg, Faculty of Medicine, University of Freiburg, Hauptstr. 5, Freiburg, 
      D-79104, Germany.
FAU - Fiebich, Bernd L
AU  - Fiebich BL
AD  - Neurochemistry Research Group, Department of Psychiatry and Psychotherapy, 
      Medical Center - University of Freiburg, Faculty of Medicine, University of 
      Freiburg, Hauptstr. 5, Freiburg, D-79104, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171211
PL  - United States
TA  - Glia
JT  - Glia
JID - 8806785
RN  - 0 (Aif1 protein, mouse)
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Immunologic Factors)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Microfilament Proteins)
RN  - 0 (Receptors, Prostaglandin E, EP2 Subtype)
RN  - 0 (Toll-Like Receptor 3)
RN  - 0 (Toll-Like Receptor 4)
RN  - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - F5TD010360 (Alprostadil)
RN  - HP16WVP23Y (butaprost)
RN  - O84C90HH2L (Poly I-C)
SB  - IM
MH  - Alprostadil/analogs & derivatives/pharmacology
MH  - Animals
MH  - Calcium-Binding Proteins/metabolism
MH  - Cells, Cultured
MH  - Cerebral Cortex/drug effects/immunology/pathology
MH  - Hippocampus/drug effects/*immunology/pathology
MH  - Immunity, Innate/physiology
MH  - Immunologic Factors/pharmacology
MH  - Inflammation/drug therapy/*metabolism/pathology
MH  - Lipopolysaccharides
MH  - Mice, Inbred C57BL
MH  - Microfilament Proteins/metabolism
MH  - Microglia/drug effects/*immunology/pathology
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Poly I-C
MH  - Prostaglandin-Endoperoxide Synthases/metabolism
MH  - Receptors, Prostaglandin E, EP2 Subtype/agonists/*metabolism
MH  - Tissue Culture Techniques
MH  - Toll-Like Receptor 3/metabolism
MH  - Toll-Like Receptor 4/metabolism
OTO - NOTNLM
OT  - EP2 receptor
OT  - Inflammatory mediators
OT  - Microglia
OT  - OHSCs
OT  - TLR3/TLR4
EDAT- 2017/12/12 06:00
MHDA- 2018/08/31 06:00
CRDT- 2017/12/12 06:00
PHST- 2017/07/27 00:00 [received]
PHST- 2017/11/08 00:00 [revised]
PHST- 2017/11/17 00:00 [accepted]
PHST- 2017/12/12 06:00 [pubmed]
PHST- 2018/08/31 06:00 [medline]
PHST- 2017/12/12 06:00 [entrez]
AID - 10.1002/glia.23276 [doi]
PST - ppublish
SO  - Glia. 2018 Apr;66(4):708-724. doi: 10.1002/glia.23276. Epub 2017 Dec 11.