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Abstract #8879 Published in IGR 5-2

Expression of matrix metalloproteinases and their inhibitors in human trabecular meshwork cells

Pang IH; Hellberg PG; Fleenor DL; Jacobson N; Clark AF
Investigative Ophthalmology and Visual Science 2003; 44: 3485-3493


PURPOSE: Matrix metalloproteinases (MMPs) are involved in trabecular meshwork (TM) extracellular matrix metabolism and have been shown to increase aqueous outflow facility. The purpose of this study was to characterize effects of cytokines, a phorbol ester, and prostanoids on the expression of MMP-1, -2, -3, and -9 and tissue inhibitors of metalloproteinases (TIMP)-1 and -2 in cultured human TM cells. METHODS: Five human TM cell strains were treated with selected compounds. Levels of proMMPs and TIMPs in cell media were quantified by ELISA. MMP-3 activity was assayed by casein zymography. RESULTS: All human TM cell strains produced detectable basal amounts of proMMPs and TIMPs. 12-O-tetradecanoyl-phorbol-13-acetate was effective in increasing the levels of proMMP-1, -3, and -9 and TIMP-1. Its effect on proMMP-1 was concentration-dependent with an EC50 of 2-3 nm. Interleukin (IL)-1 did not affect levels of proMMP-1 and -2 or the TIMPs, but was most efficacious in increasing proMMP-3 production with an EC50 of 0.5 ng/ml. The IL-1-induced upregulation of proMMP-3 correlated with an increase in MMP-3 activity. Tumor necrosis factor- activated proMMP-3 production in some but not all cell strains. Platelet-derived growth factor-BB was generally ineffective in modulating MMP and TIMP levels. Prostaglandins E2 and F2 at 10 μm did not affect levels of proMMP-1 or -3. CONCLUSIONS: The expression of the different MMPs and TIMPs in human TM cells was independently regulated. Production of MMP-3 was maximally activated by IL-1. The IL-1-stimulated expression of MMP-3 provides a probable mechanism for IL-1-enhanced aqueous outflow.

Dr. I.H. Pang, Alcon Research, Ltd., Fort Worth, TX, USA


Classification:

2.5.1 Trabecular meshwork (Part of: 2 Anatomical structures in glaucoma > 2.5 Meshwork)
3.7 Biochemistry (Part of: 3 Laboratory methods)
3.8 Pharmacology (Part of: 3 Laboratory methods)



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