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Stromelysin (matrix metalloproteinase-3) and tissue inhibitor of metalloproteinase (TIMP-1) mRNA expression in scleritis.

Abstract：

:Scleritis is a severe and destructive inflammatory eye disease characterized by extensive extracellular matrix degradation. As in rheumatoid arthritis (RA), tissue destruction in scleritis may be mediated in part by matrix metalloproteinases such as collagenase (MMP-1) and stromelysin (MMP-3) which are normally kept in balance by endogenous inhibitors, such as tissue inhibitor of metalloproteinase (TIMP-1). To test this hypothesis, in situ hybridization was used to localize MMP-1, MMP-3 and TIMP-1 mRNA in diseased and normal scleral tissue using digoxigenin labelled probes. Strong expression of MMP-3 and TIMP-1 mRNA, but not MMP-1, was observed in the diseased scleral tissue. Infiltrating inflammatory cells such as macrophages and scleral fibroblasts were the primary source of MMP-3 and TIMP-1 expression. There was also relatively less TIMP-1 compared with MMP-3 mRNA expression in the inflammatory cells in scleritis tissue. In order to study regulation of metalloproteinase expression in ocular cells the authors established human scleral fibroblasts (HSF) in primary culture. Northern blot analysis was performed on total RNA extracted from HSF grown in serum free media. MMP-1 MMP-3 and TIMP-1 were constitutively expressed in these cells. Stimulation of HSF with pro-inflammatory cytokines likely to be present in scleritis, such as interleukin-1 (IL-1) and tumor necrosis factor (TNF), significantly induced MMP-3 and TIMP-1 mRNA expression. Using culture supernatants derived from the same cytokine stimulated scleral fibroblast the authors were able to detect MMP-3 protein production by Western blot analysis. They conclude that matrix metalloproteinase-3 mRNAs are present in scleritis tissue and may be induced by cytokines produced in the inflammatory process.

journal_name

Ocul Immunol Inflamm

journal_title

Ocular immunology and inflammation

authors

Girolamo ND,McCluskey PJ,Lloyd A,Wakefield D

doi

10.3109/09273949509069111

subject

Has Abstract

pub_date

1995-01-01 00:00:00

pages

181-94

issue

eissn

0927-3948

issn

1744-5078

journal_volume

pub_type

杂志文章

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Stromelysin (matrix metalloproteinase-3) and tissue inhibitor of metalloproteinase (TIMP-1) mRNA expression in scleritis.