PMID- 12147614
OWN - NLM
STAT- MEDLINE
DCOM- 20020807
LR  - 20061115
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 43
IP  - 8
DP  - 2002 Aug
TI  - Modulation of matrix metalloproteinase and TIMP-1 expression by cytokines in 
      human RPE cells.
PG  - 2767-73
AB  - PURPOSE: The balance between matrix metalloproteinases (MMPs) and tissue 
      inhibitors of MMPs (TIMPs) is crucial for homeostasis of ocular extracellular 
      matrices. To assess altered MMP activity as a determinant in the migration of 
      human retinal pigment epithelial (RPE) cells, expression characteristics of 
      several MMPs and TIMP-1 in RPE cell cultures were investigated. METHODS: 
      Expression studies were performed with RT-PCR, ELISA, and immunofluorescence 
      analysis. Secretion of MMP-2 was demonstrated by zymography. Migration of 
      cytokine-stimulated RPE cells was evaluated with microporous membranes of 
      permeable chambers. RESULTS: MMP-1, -2, -3, and -9; MT2-MMP; and TIMP-1 were 
      expressed in cultured RPE cells. MMP-2 was detected on the cell surface and in 
      secreted inactive and active forms. TGF-beta(2), IL-1beta, and TNF-alpha enhanced 
      secretion of MMP-1, -2, and -3. TGF-beta(2) also stimulated MT2-MMP cell surface 
      expression and release of TIMP-1. The mRNA levels of MMP-1, -2, and -3 and TIMP-1 
      were markedly increased by TNF-alpha and TGF-beta(2). MMP-2 mRNA levels were also 
      upregulated by PDGF-BB. Migration of RPE cells stimulated by TGF-beta(2) or 
      PDGF-BB was inhibited in presence of a synthetic MMP inhibitor. CONCLUSIONS: 
      Proinflammatory cytokines and TGF-beta(2) play an important role in the 
      upregulation of expression of MMP-1, -2, and -3 in RPE cells and account for a 
      directional shift in the balance between MMPs and TIMPs. Facilitation of RPE cell 
      migration stimulated by cytokines (i.e., TGF-beta(2) or PDGF-BB) in ocular 
      diseases may be due to increased release of MMPs, in the presence of 
      comparatively lower levels of their inhibitors.
FAU - Eichler, Wolfram
AU  - Eichler W
AD  - University of Leipzig, Eye Hospital, Leipzig, Germany. eichwolf@rz.uni-leipzig.de
FAU - Friedrichs, Ulrike
AU  - Friedrichs U
FAU - Thies, Alexander
AU  - Thies A
FAU - Tratz, Corinna
AU  - Tratz C
FAU - Wiedemann, Peter
AU  - Wiedemann P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Cytokines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - EC 3.4.24.- (Gelatinases)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Cell Movement/physiology
MH  - Cells, Cultured
MH  - Cytokines/*pharmacology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Extracellular Matrix/metabolism
MH  - Fluorescent Antibody Technique, Indirect
MH  - Gelatinases/metabolism
MH  - Humans
MH  - Matrix Metalloproteinases/*biosynthesis/genetics
MH  - Pigment Epithelium of Eye/cytology/*drug effects/metabolism
MH  - RNA, Messenger/biosynthesis
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tissue Inhibitor of Metalloproteinase-1/*biosynthesis/genetics
MH  - Up-Regulation
EDAT- 2002/07/31 10:00
MHDA- 2002/08/08 10:01
CRDT- 2002/07/31 10:00
PHST- 2002/07/31 10:00 [pubmed]
PHST- 2002/08/08 10:01 [medline]
PHST- 2002/07/31 10:00 [entrez]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2002 Aug;43(8):2767-73.