PMID- 24339874
OWN - NLM
STAT- MEDLINE
DCOM- 20150302
LR  - 20240313
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 12
DP  - 2013
TI  - Adult human glia, pericytes and meningeal fibroblasts respond similarly to IFNy 
      but not to TGFbeta1 or M-CSF.
PG  - e80463
LID - 10.1371/journal.pone.0080463 [doi]
LID - e80463
AB  - The chemokine Interferon gamma-induced protein 10 (IP-10) and human leukocyte 
      antigen (HLA) are widely used indicators of glial activation and 
      neuroinflammation and are up-regulated in many brain disorders. These 
      inflammatory mediators have been widely studied in rodent models of brain 
      disorders, but less work has been undertaken using human brain cells. In this 
      study we investigate the regulation of HLA and IP-10, as well as other cytokines 
      and chemokines, in microglia, astrocytes, pericytes, and meningeal fibroblasts 
      derived from biopsy and autopsy adult human brain, using immunocytochemistry and 
      a Cytometric Bead Array. Interferongamma (IFNgamma) increased microglial HLA expression, 
      but contrary to data in rodents, the anti-inflammatory cytokine transforming 
      growth factor beta1 (TGFbeta1) did not inhibit this increase in HLA, nor did TGFbeta1 
      affect basal microglial HLA expression or IFNgamma-induced astrocytic HLA expression. 
      In contrast, IFNgamma-induced and basal microglial HLA expression, but not 
      IFNgamma-induced astrocytic HLA expression, were strongly inhibited by macrophage 
      colony stimulating factor (M-CSF). IFNgamma also strongly induced HLA expression in 
      pericytes and meningeal fibroblasts, which do not basally express HLA, and this 
      induction was completely blocked by TGFbeta1, but not affected by M-CSF. In 
      contrast, TGFbeta1 did not block the IFNgamma-induced increase in IP-10 in pericytes and 
      meningeal fibroblasts. These results show that IFNgamma, TGFbeta1 and M-CSF have 
      species- and cell type-specific effects on human brain cells that may have 
      implications for their roles in adult human brain inflammation.
FAU - Smith, Amy M
AU  - Smith AM
AD  - Department of Pharmacology and Clinical Pharmacology, The University of Auckland, 
      Auckland, New Zealand ; Gravida - National Research Centre for Growth and 
      Development, Auckland, New Zealand ; Centre for Brain Research, The University of 
      Auckland, Auckland, New Zealand.
FAU - Graham, E Scott
AU  - Graham ES
FAU - Feng, Sheryl Xia
AU  - Feng SX
FAU - Oldfield, Robyn L
AU  - Oldfield RL
FAU - Bergin, Peter M
AU  - Bergin PM
FAU - Mee, Edward W
AU  - Mee EW
FAU - Faull, Richard L M
AU  - Faull RL
FAU - Curtis, Maurice A
AU  - Curtis MA
FAU - Dragunow, Mike
AU  - Dragunow M
LA  - eng
GR  - G0901113/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131205
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Chemokines)
RN  - 0 (HLA-D Antigens)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 81627-83-0 (Macrophage Colony-Stimulating Factor)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adult
MH  - Astrocytes/cytology
MH  - Chemokines/metabolism
MH  - Fibroblasts/*drug effects/metabolism
MH  - Gene Expression Regulation/drug effects
MH  - HLA-D Antigens/metabolism
MH  - Humans
MH  - Interferon-gamma/*pharmacology
MH  - Macrophage Colony-Stimulating Factor/*pharmacology
MH  - Meninges/*cytology
MH  - Neuroglia/*cytology
MH  - Pericytes/*cytology
MH  - Transforming Growth Factor beta1/*pharmacology
PMC - PMC3855168
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/12/18 06:00
MHDA- 2015/03/03 06:00
PMCR- 2013/12/05
CRDT- 2013/12/17 06:00
PHST- 2013/08/14 00:00 [received]
PHST- 2013/10/02 00:00 [accepted]
PHST- 2013/12/17 06:00 [entrez]
PHST- 2013/12/18 06:00 [pubmed]
PHST- 2015/03/03 06:00 [medline]
PHST- 2013/12/05 00:00 [pmc-release]
AID - PONE-D-13-33776 [pii]
AID - 10.1371/journal.pone.0080463 [doi]
PST - epublish
SO  - PLoS One. 2013 Dec 5;8(12):e80463. doi: 10.1371/journal.pone.0080463. eCollection 
      2013.