The Inhibitory Effect of Metronidazole and Doxycycline-HCl on proMMP-3 Production in Gingival Fibroblast

Autor: Byung-Ock Kim, Sang-Mok Kim, Ki-Jung Lim, Hak-Joo Kim, Kyung-Yoon Han
Rok vydání: 2000
Předmět:
Zdroj: The Journal of the Korean Academy of Periodontology. 30:335
ISSN: 0250-3352
DOI: 10.5051/jkape.2000.30.2.335
Popis: Matrix metalloproteinases(MMP) are a family of proteolytic enzymes that mediate the degradation of extracellular matrix macromolecules, including interstitial and basement membrane collagens, fibronectin, laminin, and proteoglycan core protein. The major cell types(fibroblasts, keratinocytes, endothelial cells, and macrophages) in periodontal tissue are capable of responding to growth factors and cytokines, as well as to products released from the microbial flora by induction of transcription of one or more MMP genes1). These MMPs share some common properties: 1) secretion from the cell in a latent form(proenzyme) with its subsequent activation in the extracellualr space; 2) containing zinc cation at the active site; 3) inhibition by chelators of calcium(e.g., EDTA), and zinc(e.g., 1, 10 phenanthroline); 4) inhibition by tissue inhibitors of metalloproteinases(TIMP); and 5) degrading at least one component of the extracellular matrix(e.g., collagen)2). One prominent member of these MMPs, MMP-3(stromelysin-1) is capable of degrading the numerous extracellular matrix macromolecules(ECM) including fibronectin, laminin, proteoglycan core protein, collagen IV, V, IX, X, and elastin3). Increase of MMP-3 activity associated with several chronic inflammatory disease appear to be the result of specific inductive mechanisms. One of the mediators in induction of MMP-3 is interleukin-1(IL-1), cell product that has important regulatory functions mediating the body's response to microbial invasion, inflammation, and tissue injury4,5,6,7). Especially, IL-1 is thought to play a important role in the tissue destruction associated with inflammatory diseases such as rheumatoid arthritis and periodontal disease8,9). As periodontitis is specifically associated with the destruction of periodontal connective tissues, it is closely related to both IL-1 and MMPs. Gingivitis can trigger the initial cascade of periodontal destruction. The human gingival fibroblast is prominent cell type in the gingival connective tissue and products cytokines inducted by microbial infection in periodontal disease. In the periodontal disease, the upregulation of MMP expression in response to locally released IL-1 may provide one component of this pathologic process. IL-1 has been identified in both the gingiva and gingival crevicular fluids of periodontitis patients10,11). In Vitro, fibrob
Databáze: OpenAIRE