PMID- 10207013
OWN - NLM
STAT- MEDLINE
DCOM- 19990520
LR  - 20220408
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 17
DP  - 1999 Apr 23
TI  - Inflammatory cytokines and oxidized low density lipoproteins increase endothelial 
      cell expression of membrane type 1-matrix metalloproteinase.
PG  - 11924-9
AB  - We investigated whether inflammatory cytokines or oxidized low density 
      lipoproteins (Ox-LDL) present in human atheroma modulate extracellular matrix 
      degradation by inducing membrane type 1-matrix metalloproteinase (MT1-MMP) 
      expression. Cultured human endothelial cells (EC) constitutively expressed 
      MT1-MMP mRNA and protein with enzymatic activity. Tumor necrosis factor-alpha 
      (TNF-alpha), interleukin-1alpha, or interleukin-1beta caused a time-dependent 
      increase in the steady-state MT1-MMP mRNA levels within 4 h of exposure, peaking 
      about 4-fold by 6 h, and remaining elevated for 12 h. Increased MT1-MMP mRNA 
      correlated with a 2.5-fold increase in MT1-MMP protein in EC membranes. Ox-LDL 
      also increased MT1-MMP mRNA levels that varied with the duration of exposure and 
      degree of LDL oxidation. The increase in MT1-MMP mRNA occurred within 6 h of 
      exposure to Ox-LDL and peaked over 3-fold by 6 h. Ox-LDL, but not native LDL, 
      increased MT1-MMP protein by 2-fold in EC membranes. A combination of TNF-alpha 
      and Ox-LDL was additive in increasing MT1-MMP expression. Nuclear run-on assays 
      showed that TNF-alpha or Ox-LDL augmented steady-state mRNA levels by increased 
      transcription of the MT1-MMP gene. These findings indicate that activation of EC 
      by inflammatory cytokines and/or Ox-LDL increase MT1-MMP expression. Since 
      MT1-MMP promotes matrix degradation by activating pro-MMP-2, these results 
      suggest a novel mechanism whereby cytokines or Ox-LDL may influence extracellular 
      matrix remodeling.
FAU - Rajavashisth, T B
AU  - Rajavashisth TB
AD  - Atherosclerosis Research Center, Division of Cardiology, Cedars-Sinai Medical 
      Center, UCLA School of Medicine, Los Angeles, California 90048, USA. 
      rajavashisth@cshs.org
FAU - Liao, J K
AU  - Liao JK
FAU - Galis, Z S
AU  - Galis ZS
FAU - Tripathi, S
AU  - Tripathi S
FAU - Laufs, U
AU  - Laufs U
FAU - Tripathi, J
AU  - Tripathi J
FAU - Chai, N N
AU  - Chai NN
FAU - Xu, X P
AU  - Xu XP
FAU - Jovinge, S
AU  - Jovinge S
FAU - Shah, P K
AU  - Shah PK
FAU - Libby, P
AU  - Libby P
LA  - eng
GR  - HL51980/HL/NHLBI NIH HHS/United States
GR  - HL52233/HL/NHLBI NIH HHS/United States
GR  - HL58555/HL/NHLBI NIH HHS/United States
GR  - etc.
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 Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA Primers)
RN  - 0 (Interleukin-1)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (oxidized low density lipoprotein)
RN  - EC 3.4.24.- (Gelatinases)
RN  - EC 3.4.24.- (Matrix Metalloproteinases, Membrane-Associated)
RN  - EC 3.4.24.- (Metalloendopeptidases)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
SB  - IM
MH  - Base Sequence
MH  - Cells, Cultured
MH  - DNA Primers
MH  - Endothelium, Vascular/cytology/*metabolism
MH  - Enzyme Activation
MH  - Gelatinases/metabolism
MH  - Gene Expression Regulation
MH  - Humans
MH  - Interleukin-1/*metabolism
MH  - Lipoproteins, LDL/*metabolism
MH  - Matrix Metalloproteinase 2
MH  - Matrix Metalloproteinases, Membrane-Associated
MH  - Metalloendopeptidases/genetics/*metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Transcription, Genetic
MH  - Tumor Necrosis Factor-alpha/*metabolism
EDAT- 1999/04/17 00:00
MHDA- 1999/04/17 00:01
CRDT- 1999/04/17 00:00
PHST- 1999/04/17 00:00 [pubmed]
PHST- 1999/04/17 00:01 [medline]
PHST- 1999/04/17 00:00 [entrez]
AID - S0021-9258(19)73514-5 [pii]
AID - 10.1074/jbc.274.17.11924 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Apr 23;274(17):11924-9. doi: 10.1074/jbc.274.17.11924.