IL 1 REGULATION OF MMP GENES IN GINGIVAL FIBROBLASTS

性状（改编自研究者摘要）：白细胞介素-1（IL-1） 刺激金属蛋白酶（MMP，例如胶原酶和 基质溶解素），因此与牙龈成纤维细胞的软 与牙周炎相关的组织破坏。 虽然精确的 IL-1诱导MMP基因转录的机制尚不完全清楚， 阐明，证据表明，IL-1的作用是介导的， 多种转录因子可能与启动子相互作用， 复杂和细胞特异性的方式。 这项建议的具体目标是：1） 以鉴定与转录因子特异性相互作用的转录因子， IL-1后胶原酶和基质溶解素基因的启动子区 刺激牙龈成纤维细胞; 2）确定因素的作用 在调节胶原酶转录的具体目标1中确定 和/或溶基质素基因;和，3）进一步 表征、克隆或纯化任何先前未知的因子 在具体目标1中确定，并显示在 MMP基因的调控。 这些具体目标将通过 使用DNA酶足迹/甲基化干扰和瞬时 转染实验以系统地剖析搜索中的启动子 调节元件和结合复合物的结合。 除了提供 关于MMPs生产如何调节的重要新信息，这些 研究还可能确定治疗药物的新的潜在靶点， 牙周炎

DESCRIPTION (Adapted from investigator's Abstract): 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 the regulation of MMP genes. These specific aims will be accomplished through the use of DNAse footprinting/methylation interference and transient transfection experiments to systematically dissect the promoters in search of regulatory 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.