HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Eichler, W. Articles by Wiedemann, P. Search for Related Content PubMed PubMed Citation Articles by Eichler, W. Articles by Wiedemann, P.

Modulation of Matrix Metalloproteinase and TIMP-1 Expression by Cytokines in Human RPE Cells

From the University of Leipzig, Eye Hospital, Leipzig, Germany.

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-ß₂, IL-1ß, and TNF- enhanced secretion of MMP-1, -2, and -3. TGF-ß₂ 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- and TGF-ß₂. MMP-2 mRNA levels were also upregulated by PDGF-BB. Migration of RPE cells stimulated by TGF-ß₂ or PDGF-BB was inhibited in presence of a synthetic MMP inhibitor.

CONCLUSIONS. Proinflammatory cytokines and TGF-ß₂ 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-ß₂ or PDGF-BB) in ocular diseases may be due to increased release of MMPs, in the presence of comparatively lower levels of their inhibitors.

This article has been cited by other articles:

				M. Hollborn, C. Stathopoulos, A. Steffen, P. Wiedemann, L. Kohen, and A. Bringmann Positive Feedback Regulation between MMP-9 and VEGF in Human RPE Cells Invest. Ophthalmol. Vis. Sci., September 1, 2007; 48(9): 4360 - 4367. [Abstract] [Full Text] [PDF]

				S. Elliot, P. Catanuto, W. Stetler-Stevenson, and S. W. Cousins Retinal Pigment Epithelium Protection from Oxidant-Mediated Loss of MMP-2 Activation Requires Both MMP-14 and TIMP-2. Invest. Ophthalmol. Vis. Sci., April 1, 2006; 47(4): 1696 - 1702. [Abstract] [Full Text] [PDF]

				O. Strauss The Retinal Pigment Epithelium in Visual Function Physiol Rev, July 1, 2005; 85(3): 845 - 881. [Abstract] [Full Text] [PDF]

				K. A. Howes, Y. Liu, J. L. Dunaief, A. Milam, J. M. Frederick, A. Marks, and W. Baehr Receptor for Advanced Glycation End Products and Age-Related Macular Degeneration Invest. Ophthalmol. Vis. Sci., October 1, 2004; 45(10): 3713 - 3720. [Abstract] [Full Text] [PDF]

				N. Strunnikova, C. Zhang, D. Teichberg, S. W. Cousins, J. Baffi, K. G. Becker, and K. G. Csaky Survival of Retinal Pigment Epithelium after Exposure to Prolonged Oxidative Injury: A Detailed Gene Expression and Cellular Analysis Invest. Ophthalmol. Vis. Sci., October 1, 2004; 45(10): 3767 - 3777. [Abstract] [Full Text] [PDF]