title: Induction of dental pulp fibroblast matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 gene expression by interleukin-1alpha and tumor necrosis factor-alpha through a prostaglandin-dependent pathway.
abstract: Matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) are involved in the degradation of extracellular matrix in many inflammatory diseases. Little is known regarding the expression of these mediators in dental pulp fibroblasts. The effects of proinflammatory cytokines (interleukin (IL)-1alpha and tumor necrosis factor-alpha (TNF-alpha)) and prostaglandin E2 (PGE2) on pulp fibroblast MMP-1 and TIMP-1 gene expression were investigated. Northern hybridization showed that IL-1alpha and TNF-alpha induced significant MMP-1 gene expression, with only little effect on TIMP-1 gene. Exogenous PGE2, however, upregulated TIMP-1 mRNA synthesis but not MMP-1. Concomitant addition of IL-1alpha and PGE2 or TNF-alpha and PGE2 suppressed MMP-1 mRNA production, compared with the groups treated with IL-1alpha or TNF-alpha alone. In contrast, PGE2 enhanced the upregulatory effects of TIMP-1 mRNA by IL-1alpha or TNF-alpha. Furthermore, cytokine stimulation of MMP-1 and TIMP-1 gene expressions can be enhanced or blocked by indomethacin, respectively, and reversed by exogenous PGE2. These results suggested that cytokine-stimulated MMP-1 and TIMP-1 gene expression in dental pulp fibroblasts was mediated, at least in part, by a prostaglandin-dependent pathway. The differential regulation of IL-1alpha or TNF-alpha-induced MMP-1 and TIMP-1 mRNA synthesis, as well as the direct upregulation of TIMP-1 gene expression by PGE2, also implied that prostaglandin may serve as a protective mechanism from excessive tissue breakdown during pulpitis.
authors.affiliation: School of Dentistry, Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei.
authors.forename: S K
authors.initials: SK
authors.lastname: Lin
authors.forename: C C
authors.initials: CC
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Huang
authors.forename: J J
authors.initials: JJ
authors.lastname: Lee
authors.forename: C P
authors.initials: CP
authors.lastname: Chiang
authors.forename: W H
authors.initials: WH
authors.lastname: Lan
authors.forename: C Y
authors.initials: CY
authors.lastname: Hong
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D015152:Blotting, Northern; D018929:Cell Culture Techniques; D003782:Dental Pulp / Q000166:cytology / Q000201:enzymology*; D015232:Dinoprostone / Q000494:pharmacology*; D005347:Fibroblasts / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D018836:Inflammation Mediators / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D020781:Matrix Metalloproteinase 1 / Q000187:drug effects / Q000235:genetics*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000187:drug effects / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018836:Inflammation Mediators; D007375:Interleukin-1; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D020781:Matrix Metalloproteinase 1; D015232:Dinoprostone; D007213:Indomethacin