PMID- 10217399
OWN - NLM
STAT- MEDLINE
DCOM- 19990601
LR  - 20190621
IS  - 0014-5793 (Print)
IS  - 0014-5793 (Linking)
VI  - 448
IP  - 1
DP  - 1999 Apr 1
TI  - Reprogramming of TIMP-1 and TIMP-3 expression profiles in brain microvascular 
      endothelial cells and astrocytes in response to proinflammatory cytokines.
PG  - 9-14
AB  - Cytokine-dependent regulation of tissue inhibitors of metalloproteinases (TIMPs) 
      expression provides an important mechanism for controlling the activity of matrix 
      metalloproteinases. We present data indicating that during inflammatory processes 
      TIMP-1 and TIMP-3 may be involved in the proteolytic remodeling of subendothelial 
      basement membrane of the brain microvascular system, a key step during leukocyte 
      migration into the brain perivascular tissue. In brain endothelial cells the 
      expression of TIMP-1 is dramatically up-regulated by major proinflammatory 
      cytokines, with the combination of interleukin-1beta (IL-1beta) and tumor 
      necrosis factor-alpha (TNF alpha) exhibiting the strongest synergistic 
      stimulation. Simultaneously, IL-1beta/TNF alpha almost completely blocks TIMP-3 
      expression. Both synergistic effects are dose-dependent within the concentration 
      range 0.05-5 ng/ml of both cytokines and correlate with the expression of 
      inducible nitric oxide synthase, an endothelial cell activation marker. 
      Down-regulation of TIMP-3 expression is also detected in astrocytes treated with 
      TNF alpha or IFN-gamma whereas oncostatin M as well as TNF alpha up-regulate 
      TIMP-1 mRNA level. We propose that the cytokine-modified balance between TIMP-1 
      and TIMP-3 expression provides a potential mechanism involved in the regulation 
      of microvascular basement membrane proteolysis.
FAU - Bugno, M
AU  - Bugno M
AD  - Institute of Molecular Biology, Jagiellonian University, Cracow, Poland. 
      marcinb@arches.uga.edu
FAU - Witek, B
AU  - Witek B
FAU - Bereta, J
AU  - Bereta J
FAU - Bereta, M
AU  - Bereta M
FAU - Edwards, D R
AU  - Edwards DR
FAU - Kordula, T
AU  - Kordula T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - FEBS Lett
JT  - FEBS letters
JID - 0155157
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interleukin-1)
RN  - 0 (OSM protein, human)
RN  - 0 (Peptides)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-3)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 106956-32-5 (Oncostatin M)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 1.14.13.39 (NOS2 protein, human)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, rat)
SB  - IM
MH  - Animals
MH  - Astrocytes/cytology/drug effects/enzymology
MH  - Brain/cytology/enzymology
MH  - Cells, Cultured
MH  - Cytokines/*metabolism/pharmacology
MH  - Endothelium, Vascular/cytology
MH  - Gene Expression Regulation, Enzymologic/*drug effects
MH  - Humans
MH  - Inflammation Mediators/pharmacology
MH  - Interferon-gamma/metabolism/pharmacology
MH  - Interleukin-1/metabolism/pharmacology
MH  - Nitric Oxide Synthase/genetics
MH  - Nitric Oxide Synthase Type II
MH  - Oncostatin M
MH  - Peptides/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Tissue Inhibitor of Metalloproteinase-1/*genetics
MH  - Tissue Inhibitor of Metalloproteinase-3/*genetics
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/metabolism/pharmacology
MH  - Vascular Cell Adhesion Molecule-1/genetics
EDAT- 1999/04/27 00:00
MHDA- 1999/04/27 00:01
CRDT- 1999/04/27 00:00
PHST- 1999/04/27 00:00 [pubmed]
PHST- 1999/04/27 00:01 [medline]
PHST- 1999/04/27 00:00 [entrez]
AID - S0014-5793(99)00323-3 [pii]
AID - 10.1016/s0014-5793(99)00323-3 [doi]
PST - ppublish
SO  - FEBS Lett. 1999 Apr 1;448(1):9-14. doi: 10.1016/s0014-5793(99)00323-3.