Human Mast Cell-derived Gelatinase B (Matrix Metalloproteinase-9) is Regulated by Inflammatory Cytokines: Role in Cell Migration.
From: Inflammatory Diseases Research Unit, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: Aug 2006
- ISSN: 0022-1767
- Volume: 177
- Issue: 4
- Pages: 2638-50
- Medium: Print
- Language: English
- Citation (JAMA): Di Girolamo Nick, Indoh Ikuko, Jackson Nicole, et al. Human Mast Cell-derived Gelatinase B (Matrix Metalloproteinase-9) is Regulated by Inflammatory Cytokines: Role in Cell Migration.. J. Immunol. Aug 2006;177:2638-50
Abstract
Mast cells are key effectors in the pathogenesis of inflammatory and tissue destructive diseases such as rheumatoid arthritis (RA). These cells contain specialized secretory granules loaded with bioactive molecules including cytokines, growth factors, and proteases that are released upon activation. This study investigated the regulation of matrix metalloproteinase MMP-9 (gelatinase B) in human mast cells by cytokines that are known to be involved in the pathogenesis of RA. Immunohistochemical staining of synovial tissue showed abundant expression of MMP-9 by synovial tissue mast cells in patients with RA but not in normal controls. The expression, activity, and production of MMP-9 in mast cells was confirmed by RT-PCR, zymography, and Western blotting using cord blood-derived human mast cells (CB-HMC). Treatment of CB-HMC with TNF-alpha significantly increased the expression of MMP-9 mRNA and up-regulated the activity of MMP-9 in a time- and dose-dependent manner. By contrast, IFN-gamma inhibited MMP-9 mRNA and protein expression. The cytokine-mediated regulation of MMP-9 was also apparent in the human mast cell line (HMC-1) and in mouse bone marrow-derived mast cells. Furthermore, TNF-alpha significantly increased the invasiveness of CB-HMC across Matrigel-coated membranes while the addition of IFN-gamma, rTIMP-1, or pharmacological MMP inhibitors significantly reduced this process. These observations suggest that MMP-9 is not a stored product in mast cells but these cells are capable of producing this enzyme under inflammatory conditions that may facilitate the migration of mast cell progenitors to sites of inflammation and may also contribute to local tissue damage.
Mesh Headings (Keywords): Animals, Arthritis, Rheumatoid, Cell Line, Tumor, Cell Movement, Cells, Cultured, Collagen, Cytokines, Drug Combinations, Enzyme Induction, Female, Fetal Blood, Humans, Inflammation Mediators, Laminin, Mast Cells, Matrix Metalloproteinase 9, Membrane Proteins, Mice, Mice, Inbred BALB C, Proteoglycans, Receptors, Complement
Check for Full Text / PubMed Unique Identifier (PMID): 16888026
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