Expression of Matrix Metalloproteinases and Their Inhibitors in Human Trabecular Meshwork Cells

• Published in: Investigative ophthalmology & visual science Vol. 44; no. 8; pp. 3485 - 3493
• Main Authors: Pang, Iok-Hou, Hellberg, Peggy E, Fleenor, Debra L, Jacobson, Nasreen, Clark, Abbot F
• Format: Journal Article
• Language: English
• Published: Rockville, MD ARVO 01.08.2003; Association for Research in Vision and Ophtalmology
• Subjects: Adolescent; Becaplermin; Biological and medical sciences; Cells, Cultured; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Eye and associated structures. Visual pathways and centers. Vision; Fundamental and applied biological sciences. Psychology; Humans; Infant; Interleukin-1 - pharmacology; Matrix Metalloproteinases - biosynthesis; Middle Aged; Platelet-Derived Growth Factor - pharmacology; Proto-Oncogene Proteins c-sis; Tetradecanoylphorbol Acetate - pharmacology; Tissue Inhibitor of Metalloproteinase-1 - biosynthesis; Tissue Inhibitor of Metalloproteinase-2 - biosynthesis; Trabecular Meshwork - cytology; Trabecular Meshwork - drug effects; Trabecular Meshwork - enzymology; Tumor Necrosis Factor-alpha - pharmacology; Vertebrates: nervous system and sense organs; Human; Eye; Visual system; Cell culture; Extracellular matrix; Inhibitor; Gene expression; Cell; Metalloproteins; Trabecular Meshwork
• ISSN: 0146-0404; 1552-5783; 1552-5783
• DOI: 10.1167/iovs.02-0756

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. 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. 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 EC(50) of 2 to 3 nM. Interleukin (IL)-1alpha did not affect levels of proMMP-1 and -2 or the TIMPs, but was most efficacious in increasing proMMP-3 production with an EC(50) of 0.5 ng/mL. The IL-1alpha-induced upregulation of proMMP-3 correlated with an increase in MMP-3 activity. Tumor necrosis factor-alpha 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 E(2) and F(2alpha) at 10 micro M did not affect levels of proMMP-1 or -3. The expression of the different MMPs and TIMPs in human TM cells was independently regulated. Production of MMP-3 was maximally activated by IL-1alpha. The IL-1alpha-stimulated expression of MMP-3 provides a probable mechanism for IL-1alpha-enhanced aqueous outflow.