PMID- 21656856
OWN - NLM
STAT- MEDLINE
DCOM- 20111129
LR  - 20211020
IS  - 1098-1136 (Electronic)
IS  - 0894-1491 (Print)
IS  - 0894-1491 (Linking)
VI  - 59
IP  - 10
DP  - 2011 Oct
TI  - CXCR2 signaling protects oligodendrocyte progenitor cells from 
      IFN-gamma/CXCL10-mediated apoptosis.
PG  - 1518-28
LID - 10.1002/glia.21195 [doi]
AB  - Infiltration of activated lymphocytes into the central nervous system (CNS) is 
      potentially harmful by damaging resident cells through release of cytokines. 
      Among these is IFN-gamma that is secreted by activated natural killer (NK) cells and 
      T lymphocytes and can exert a cytotoxic effect on resident glial populations 
      including oligodendrocytes. Here we show that treatment of mouse oligodendrocyte 
      progenitor cell (OPC)-enriched cultures with IFN-gamma resulted in a dose-dependent 
      increase in apoptosis. IFN-gamma-induced apoptosis is mediated, in part, through 
      induction of the CXC chemokine ligand 10 (CXCL10; IP-10) from cultured OPCs. 
      Treatment of OPCs with CXCL10 resulted in cell death in a concentration-dependent 
      manner and IFN-gamma-treatment of CXCL10-/- OPCs resulted in >50% reduction in cell 
      death. Further, treatment of CXCR3-/- OPC cultures with either IFN-gamma or CXCL10 
      resulted in reduced cell death supporting an important role for CXCL10 signaling 
      in IFN-gamma-mediated OPC apoptosis. Data is also provided demonstrating that 
      signaling through CXCR2 protects either IFN-gamma or CXCL10-treated OPC cultures from 
      apoptosis and this effect is abolished in CXCR2-/- OPCs. CXCR2-mediated 
      protection from apoptosis is associated with impaired cleavage of caspase 3 and 
      elevated expression of the anti-apoptotic protein Bcl-2. These findings 
      demonstrate a previously unappreciated role for CXCL10 in contributing to 
      neuropathology by promoting oligodendrocyte apoptosis and emphasize the potential 
      relevance in targeting CXCL10 in treating human demyelinating diseases including 
      multiple sclerosis (MS).
CI  - Copyright (c) 2011 Wiley-Liss, Inc.
FAU - Tirotta, Emanuele
AU  - Tirotta E
AD  - Department of Molecular Biology and Biochemistry, University of California, 
      Irvine, California 92697-3900, USA.
FAU - Ransohoff, Richard M
AU  - Ransohoff RM
FAU - Lane, Thomas E
AU  - Lane TE
LA  - eng
GR  - R01 NS032151/NS/NINDS NIH HHS/United States
GR  - R01 NS041249/NS/NINDS NIH HHS/United States
GR  - R01NS41249/NS/NINDS NIH HHS/United States
GR  - R01NS32151/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110608
PL  - United States
TA  - Glia
JT  - Glia
JID - 8806785
RN  - 0 (Antigens)
RN  - 0 (Chemokine CXCL10)
RN  - 0 (Cxcl10 protein, mouse)
RN  - 0 (Cxcr3 protein, mouse)
RN  - 0 (Proteoglycans)
RN  - 0 (Receptors, CXCR3)
RN  - 0 (Receptors, Interleukin-8B)
RN  - 0 (chondroitin sulfate proteoglycan 4)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Antigens/metabolism
MH  - Apoptosis/*drug effects/genetics/physiology
MH  - Cells, Cultured
MH  - Chemokine CXCL10/deficiency/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Enzyme-Linked Immunosorbent Assay/methods
MH  - In Situ Nick-End Labeling/methods
MH  - Interferon-gamma/*pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Oligodendroglia/*drug effects/metabolism
MH  - Proteoglycans/metabolism
MH  - Receptors, CXCR3/genetics/metabolism
MH  - Receptors, Interleukin-8B/genetics/*metabolism
MH  - Signal Transduction/drug effects/genetics
MH  - Stem Cells/*drug effects/metabolism
MH  - Time Factors
PMC - PMC5029281
MID - NIHMS816323
EDAT- 2011/06/10 06:00
MHDA- 2011/12/13 00:00
PMCR- 2016/09/20
CRDT- 2011/06/10 06:00
PHST- 2010/11/30 00:00 [received]
PHST- 2011/05/12 00:00 [revised]
PHST- 2011/05/16 00:00 [accepted]
PHST- 2011/06/10 06:00 [entrez]
PHST- 2011/06/10 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
PHST- 2016/09/20 00:00 [pmc-release]
AID - 10.1002/glia.21195 [doi]
PST - ppublish
SO  - Glia. 2011 Oct;59(10):1518-28. doi: 10.1002/glia.21195. Epub 2011 Jun 8.