IL-1 REGULATION OF MMP GENES--HUMAN GINGIVAL FIBROBLASTS

IL-1对MMP基因的调控--人牙龈成纤维细胞

• 批准号: 2132941
• 负责人: RUTH C BORGHAEI
• 金额: $ 3.49万
• 依托单位: PHILADELPHIA COLLEGE OF OSTEOPATHIC MED
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-15 至 1997-07-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2132941
• 关键词: DNA binding protein; DNA footprinting; affinity chromatography; chloramphenicol acetyltransferase; collagenase; complementary DNA; crosslink; enzyme induction /repression; fibroblasts; gel mobility shift assay; genetic library; genetic promoter element; genetic regulation; gingiva; human subject; interleukin 1; ion exchange chromatography; molecular cloning; molecular site; protein purification; site directed mutagenesis; stromelysin; tissue /cell culture; transcription factor; transfection

Interleukin-1 (IL-1) stimulates production of metalloproteinases (MMPs. e.g. collagenase and stromelysin) by gingival fibroblasts. and has therefore been linked to soft tissue destruction associated with periodontitis. Although the precise mechanisms of IL-1 induction of MMP gene transcription have not been fully elucidated, evidence suggests that the effects of IL-1 are mediated by multiple transcription factors which may interact with the promoters in complex and cell specific ways. The specific aims of this proposal are: 1) to identify transcription factors that specifically interact with the promoter regions of collagenase and stromelysin genes following IL-1 stimulation of gingival fibroblasts; 2) to determine the role(s) of factors identified in Specific Aim #1 in regulating transcription of collagenase and/or stromelysin genes in response to IL-1; and 3) to further characterize and clone or purify any previously unknown factor(s) identified in Specific Aim #1 and shown to play a significant role in regulation of the MMP genes. These specific aims will be accomplished through the use of standard molecular biology techniques including electrophoretic mobility shift assays (EMSA), DNAse footprinting and transient transfection experiments to systematically dissect the promoters In search of regulator elements and binding complexes. In addition to providing important new information about how production of MMPs is regulated. these studies might also identify new potential targets for therapeutic agents for periodontitis.

白细胞介素-1 （IL-1）刺激金属蛋白酶（MMPs）的产生。