title: Regulation of tissue inhibitors of metalloproteinase-1 gene expression by cytokines in human gingival fibroblasts.
abstract: Tissue inhibitors of metalloproteinase (TIMP) are important participants in various physiological processes that involve tissues remodeling. They help maintain a delicate balance between physiological degradation and synthesis of the extracellular matrix. A better understanding of TIMP activity will be helpful in understanding the etiology of periapical lesions and their means of treatment. The fibroblast is a prominent cellular component of the periapical tissues. The potential implications of cytokine-mediated tissue destruction still remain to be elucidated. The purpose of this study was to determine the effects of interleukin (IL)-1alpha and transforming growth factor (TGF)-beta on the expressing of TIMP-1 by primary gingival fibroblast cultures. After exposure to cytokines for 8 h, total RNA in gingival fibroblasts was isolated and evaluated by reverse-transcriptase polymerase chain reaction. Densitometric analysis of the TIMP-1 mRNA gene expression, after normalization by beta-actin, demonstrated that exposure to IL-1alpha resulted in a decreased level of TIMP-1 mRNA compared with the control groups. However, the TIMP-1 mRNA was up-regulated by TGF-beta. In addition, when the cells were cultured in combination with TGF-beta (1 ng/ml) and IL-1alpha for 8 h, the level of TIMP-1 mRNA was dramatically reduced. These results demonstrated that in human periapical tissue cytokines differentially and specifically regulate expression of TIMP-1 mRNA. An understanding of the actions of cytokines on gingival fibroblasts may result in new therapies to augment current treatment of periapical lesions.
authors.affiliation: Department of Medical Research, Show Chwan Memorial Hospital, Changhua, Taiwan.
authors.forename: Yu-Yen
authors.initials: YY
authors.lastname: Yang
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Tsai
authors.forename: Shiou-Chin
authors.initials: SC
authors.lastname: Lu
authors.forename: Ya-Fang
authors.initials: YF
authors.lastname: Huang
authors.forename: Yu-Chao
authors.initials: YC
authors.lastname: Chang
mesh_terms: D002478:Cells, Cultured; D005347:Fibroblasts / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic; D005881:Gingiva / Q000166:cytology / Q000201:enzymology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology* / Q000502:physiology; D010486:Periapical Tissue / Q000201:enzymology*; D012333:RNA, Messenger / Q000032:analysis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000494:pharmacology* / Q000502:physiology; D015854:Up-Regulation
chemical_list: D007375:Interleukin-1; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta