PMID- 16316466
OWN - NLM
STAT- MEDLINE
DCOM- 20060216
LR  - 20181113
IS  - 1471-2202 (Electronic)
IS  - 1471-2202 (Linking)
VI  - 6
DP  - 2005 Nov 29
TI  - Astrocyte reactivity to Fas activation is attenuated in TIMP-1 deficient mice, an 
      in vitro study.
PG  - 68
AB  - BACKGROUND: Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a 
      multifunctional secreted protein with pleiotropic actions, including the 
      inhibition of matrix metalloproteinases (MMPs), cell death/survival and growth 
      promoting activities. After inflammatory challenge, the levels of TIMP-1 are 
      highly and selectively upregulated in astrocytes among glial cells, but little is 
      know about its role in these neural cells. We investigated the influence of 
      TIMP-1 null mutation in the reactivity of cultured astrocytes to pro-inflammatory 
      stimuli with TNF-alpha and anti-Fas antibody. RESULTS: When compared to WT, 
      mutant astrocytes displayed an overall increased constitutive gelatinase 
      expression and were less responsive to Fas-mediated upregulation of MMP-9, of 
      monocyte chemoattractant protein-1 (MCP-1) and of intercellular cell adhesion 
      molecule-1 (ICAM-1), all markers of astrocyte inflammatory response. In contrast, 
      TNF-alpha treatment induced all these factors similarly regardless of the 
      astrocyte genotype. The incorporation of 3H-thymidin, a marker of cell 
      proliferation, increased in wild-type (WT) astrocytes after treatment with 
      anti-Fas antibody or recombinant TIMP-1 but not in mutant astrocytes. Finally, 
      lymphocyte chemotaxis was differentially regulated by TNF-alpha in WT and TIMP-1 
      deficient astrocytes. CONCLUSION: We provide evidence that the alteration of the 
      MMP/TIMP balance in astrocytes influences their reactivity to pro-inflammatory 
      stimuli and that Fas activation modulates the expression of members of the 
      MMP/TIMP axis. We hypothesise that the Fas/FasL transduction pathway and the 
      MMP/TIMP system interact in astrocytes to modulate their inflammatory response to 
      environmental stimuli.
FAU - Ogier, Crystel
AU  - Ogier C
AD  - Neurobiologie des Interactions Cellulaires et Neurophysiopathologie, CNRS UMR 
      6184, Universite de la Mediterranee, Faculte de Medecine de Marseille, IFR Jean 
      Roche, Bd, Pierre Dramard, 13916, Marseille cedex 20, France. 
      ogier.c@jean-roche.univ-mrs.fr
FAU - Creidy, Rita
AU  - Creidy R
FAU - Boucraut, Jose
AU  - Boucraut J
FAU - Soloway, Paul D
AU  - Soloway PD
FAU - Khrestchatisky, Michel
AU  - Khrestchatisky M
FAU - Rivera, Santiago
AU  - Rivera S
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20051129
PL  - England
TA  - BMC Neurosci
JT  - BMC neuroscience
JID - 100966986
RN  - 0 (Antibodies)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Fas protein, mouse)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Tetrazolium Salts)
RN  - 0 (Thiazoles)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (fas Receptor)
RN  - 10028-17-8 (Tritium)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - EUY85H477I (thiazolyl blue)
RN  - VC2W18DGKR (Thymidine)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Antibodies/adverse effects
MH  - Astrocytes/enzymology/*physiology
MH  - Blotting, Western/methods
MH  - Brain/cytology
MH  - Cell Count/methods
MH  - Cell Death/drug effects
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Electrophoretic Mobility Shift Assay/methods
MH  - Enzyme Activation/physiology
MH  - Enzyme-Linked Immunosorbent Assay/methods
MH  - Flow Cytometry/methods
MH  - Gene Expression Regulation, Developmental/*genetics
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Immunohistochemistry/methods
MH  - Intercellular Adhesion Molecule-1/metabolism
MH  - Lymphocytes/physiology
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Receptors, Tumor Necrosis Factor/immunology/*metabolism
MH  - Tetrazolium Salts
MH  - Thiazoles
MH  - Thymidine/metabolism
MH  - Tissue Inhibitor of Metalloproteinase-1/*deficiency
MH  - Tritium/metabolism
MH  - Tumor Necrosis Factor-alpha/adverse effects
MH  - fas Receptor
PMC - PMC1325973
EDAT- 2005/12/01 09:00
MHDA- 2006/02/17 09:00
PMCR- 2005/11/29
CRDT- 2005/12/01 09:00
PHST- 2005/06/24 00:00 [received]
PHST- 2005/11/29 00:00 [accepted]
PHST- 2005/12/01 09:00 [pubmed]
PHST- 2006/02/17 09:00 [medline]
PHST- 2005/12/01 09:00 [entrez]
PHST- 2005/11/29 00:00 [pmc-release]
AID - 1471-2202-6-68 [pii]
AID - 10.1186/1471-2202-6-68 [doi]
PST - epublish
SO  - BMC Neurosci. 2005 Nov 29;6:68. doi: 10.1186/1471-2202-6-68.