PMID- 11549724
OWN - NLM
STAT- MEDLINE
DCOM- 20011004
LR  - 20191023
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 21
IP  - 18
DP  - 2001 Sep 15
TI  - P2X7-like receptor activation in astrocytes increases chemokine monocyte 
      chemoattractant protein-1 expression via mitogen-activated protein kinase.
PG  - 7135-42
AB  - Leukocyte infiltration in the CNS after trauma or inflammation is triggered in 
      part by upregulation of the chemokine, monocyte chemoattractant protein-1 
      (MCP-1), in astrocytes. However the signals that induce the upregulation of MCP-1 
      in astrocytes are unknown. We have investigated the roles for ATP P2X7 receptor 
      activation because ATP is an intercellular signaling transmitter that is released 
      in both trauma and inflammation and P2X7 receptors are involved in immune system 
      signaling. Astrocytes in primary cell culture and acutely isolated from the 
      hippocampus were immunopositive for P2X7 receptors. In astrocyte cultures, 
      application of the selective P2X7 agonist, benzoyl-benzoyl ATP (Bz-ATP), 
      activated MAP kinases extracellular signal receptor-activated kinase 1 (ERK1), 
      ERK2, and p38. Purinergic antagonists depressed this activation with a profile 
      suggesting P2X7 receptors. Bz-ATP also increased MCP-1 expression in cultured 
      astrocytes, and again P2X7 antagonists prevented this increase. Blocking either 
      the ERK1/ERK2 or the p38 pathway (with PD98059 or SB203580, respectively) 
      significantly inhibited Bz-ATP-induced MCP-1 expression. Coapplication of both 
      antagonists caused a greater depression. We also tested the roles for ATP 
      receptor activation in inducing MCP-1 upregulation in corticectomy, an in vivo 
      model of trauma. This model of cortical trauma was previously shown to increase 
      MCP-1 expression in vivo principally in astrocytes. Suramin, a wide-spectrum 
      purinergic receptor antagonist, significantly depressed the rapid (3 hr) 
      trauma-induced increase in MCP-1 mRNA. These data indicate that purinergic 
      transmitter receptors in astrocytes are important in regulating chemokine 
      synthesis. The regulation of MCP-1 in astrocytes by ATP may be important in 
      mediating communication with hematopoietic inflammatory cells.
FAU - Panenka, W
AU  - Panenka W
AD  - Neuroscience Research Group, University of Calgary, Calgary, Alberta, Canada T2N 
      4N1.
FAU - Jijon, H
AU  - Jijon H
FAU - Herx, L M
AU  - Herx LM
FAU - Armstrong, J N
AU  - Armstrong JN
FAU - Feighan, D
AU  - Feighan D
FAU - Wei, T
AU  - Wei T
FAU - Yong, V W
AU  - Yong VW
FAU - Ransohoff, R M
AU  - Ransohoff RM
FAU - MacVicar, B A
AU  - MacVicar BA
LA  - eng
GR  - 2RO1-NS32151/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Chemokine CCL2)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Purinergic P2 Receptor Agonists)
RN  - 0 (Purinergic P2 Receptor Antagonists)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Purinergic P2)
RN  - 0 (Receptors, Purinergic P2X7)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Adenosine Triphosphate/analogs & derivatives/metabolism/pharmacology
MH  - Animals
MH  - Astrocytes/cytology/drug effects/*metabolism
MH  - Cells, Cultured
MH  - Cerebral Decortication
MH  - Chemokine CCL2/*biosynthesis/genetics
MH  - Dose-Response Relationship, Drug
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Hippocampus/cytology/drug effects/metabolism
MH  - Immunohistochemistry
MH  - Male
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Purinergic P2 Receptor Agonists
MH  - Purinergic P2 Receptor Antagonists
MH  - RNA, Messenger/biosynthesis
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Purinergic P2/*metabolism
MH  - Receptors, Purinergic P2X7
MH  - Signal Transduction/drug effects/physiology
MH  - p38 Mitogen-Activated Protein Kinases
PMC - PMC6762971
EDAT- 2001/09/11 10:00
MHDA- 2001/10/05 10:01
PMCR- 2002/03/15
CRDT- 2001/09/11 10:00
PHST- 2001/09/11 10:00 [pubmed]
PHST- 2001/10/05 10:01 [medline]
PHST- 2001/09/11 10:00 [entrez]
PHST- 2002/03/15 00:00 [pmc-release]
AID - 21/18/7135 [pii]
AID - 5642 [pii]
AID - 10.1523/JNEUROSCI.21-18-07135.2001 [doi]
PST - ppublish
SO  - J Neurosci. 2001 Sep 15;21(18):7135-42. doi: 10.1523/JNEUROSCI.21-18-07135.2001.