PMID- 26166618
OWN - NLM
STAT- MEDLINE
DCOM- 20160728
LR  - 20210103
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 5
DP  - 2015 Jul 13
TI  - An anti-inflammatory role for C/EBPdelta in human brain pericytes.
PG  - 12132
LID - 10.1038/srep12132 [doi]
LID - 12132
AB  - Neuroinflammation contributes to the pathogenesis of several neurological 
      disorders and pericytes are implicated in brain inflammatory processes. Cellular 
      inflammatory responses are orchestrated by transcription factors but information 
      on transcriptional control in pericytes is lacking. Because the transcription 
      factor CCAAT/enhancer binding protein delta (C/EBPdelta) is induced in a number of 
      inflammatory brain disorders, we sought to investigate its role in regulating 
      pericyte immune responses. Our results reveal that C/EBPdelta is induced in a 
      concentration- and time-dependent fashion in human brain pericytes by 
      interleukin-1beta (IL-1beta). To investigate the function of the induced C/EBPdelta in 
      pericytes we used siRNA to knockdown IL-1beta-induced C/EBPdelta expression. C/EBPdelta 
      knockdown enhanced IL-1beta-induced production of intracellular adhesion molecule-1 
      (ICAM-1), interleukin-8, monocyte chemoattractant protein-1 (MCP-1) and IL-1beta, 
      whilst attenuating cyclooxygenase-2 and superoxide dismutase-2 gene expression. 
      Altered ICAM-1 and MCP-1 protein expression were confirmed by cytometric bead 
      array and immunocytochemistry. Our results show that knock-down of C/EBPdelta 
      expression in pericytes following immune stimulation increased chemokine and 
      adhesion molecule expression, thus modifying the human brain pericyte 
      inflammatory response. The induction of C/EBPdelta following immune stimulation may 
      act to limit infiltration of peripheral immune cells, thereby preventing further 
      inflammatory responses in the brain.
FAU - Rustenhoven, Justin
AU  - Rustenhoven J
AD  - 1] Department of Pharmacology and Clinical Pharmacology [2] Centre for Brain 
      Research.
FAU - Scotter, Emma L
AU  - Scotter EL
AD  - 1] Department of Pharmacology and Clinical Pharmacology [2] Centre for Brain 
      Research.
FAU - Jansson, Deidre
AU  - Jansson D
AD  - 1] Department of Pharmacology and Clinical Pharmacology [2] Gravida National 
      Centre for Growth and Development [3] Centre for Brain Research.
FAU - Kho, Dan T
AU  - Kho DT
AD  - 1] Department of Pharmacology and Clinical Pharmacology [2] Centre for Brain 
      Research.
FAU - Oldfield, Robyn L
AU  - Oldfield RL
AD  - The University of Auckland, 1023, Auckland, New Zealand.
FAU - Bergin, Peter S
AU  - Bergin PS
AD  - 1] Centre for Brain Research [2] Lab Plus, Auckland City Hospital, 1023, 
      Auckland, New Zealand.
FAU - Mee, Edward W
AU  - Mee EW
AD  - 1] Centre for Brain Research [2] Lab Plus, Auckland City Hospital, 1023, 
      Auckland, New Zealand.
FAU - Faull, Richard L M
AU  - Faull RL
AD  - 1] Department of Anatomy with Radiology [2] Centre for Brain Research.
FAU - Curtis, Maurice A
AU  - Curtis MA
AD  - 1] Department of Anatomy with Radiology [2] Centre for Brain Research.
FAU - Graham, Scott E
AU  - Graham SE
AD  - 1] Department of Pharmacology and Clinical Pharmacology [2] Centre for Brain 
      Research.
FAU - Park, Thomas I-H
AU  - Park TI
AD  - 1] Department of Pharmacology and Clinical Pharmacology [2] Centre for Brain 
      Research.
FAU - Dragunow, Mike
AU  - Dragunow M
AD  - 1] Department of Pharmacology and Clinical Pharmacology [2] Gravida National 
      Centre for Growth and Development [3] Centre for Brain Research.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150713
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (CEBPD protein, human)
RN  - 0 (CXCL8 protein, human)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Interleukin-8)
RN  - 0 (Transcription Factors)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 142662-43-9 (CCAAT-Enhancer-Binding Protein-delta)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 1.15.1.1 (superoxide dismutase 2)
SB  - IM
MH  - Anti-Inflammatory Agents/*metabolism
MH  - Brain/metabolism/pathology
MH  - CCAAT-Enhancer-Binding Protein-delta/*metabolism
MH  - Gene Expression Regulation/physiology
MH  - Humans
MH  - Inflammation/*metabolism/pathology
MH  - Intercellular Adhesion Molecule-1/metabolism
MH  - Interleukin-1beta/metabolism
MH  - Interleukin-8/metabolism
MH  - Pericytes/*metabolism/pathology
MH  - Superoxide Dismutase/metabolism
MH  - Transcription Factors/metabolism
PMC - PMC4499812
EDAT- 2015/07/15 06:00
MHDA- 2016/07/29 06:00
PMCR- 2015/07/13
CRDT- 2015/07/14 06:00
PHST- 2014/11/06 00:00 [received]
PHST- 2015/06/01 00:00 [accepted]
PHST- 2015/07/14 06:00 [entrez]
PHST- 2015/07/15 06:00 [pubmed]
PHST- 2016/07/29 06:00 [medline]
PHST- 2015/07/13 00:00 [pmc-release]
AID - srep12132 [pii]
AID - 10.1038/srep12132 [doi]
PST - epublish
SO  - Sci Rep. 2015 Jul 13;5:12132. doi: 10.1038/srep12132.