REGULATION OF B-DEFENSIN EXPRESSION IN ORAL EPITHELIA

口腔上皮细胞中 B 防御素表达的调节

• 批准号: 6379979
• 负责人: BEVERLY A DALE-CRUNK
• 金额: $ 25.84万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-15 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6379979
• 关键词: CD14 molecule; Fusobacterium nucleatum; bacteria infection mechanism; biological signal transduction; cell differentiation; cell growth regulation; complementary DNA; defensins; dental plaque; gastrointestinal epithelium; gene expression; genetic regulation; gingiva; human tissue; interleukin 8; keratinocyte; lipopolysaccharides; messenger RNA; nuclear factor kappa beta; oral mucosa; protein structure function; tissue /cell culture

DESCRIPTION (Adapted from the Applicant's Abstract): Oral epithelia serve as a first line of defense for oral and periodontal health via innate host defense mechanisms. Human gingival epithelial cells (HGECs) express two antimicrobial peptides of the beta-defensin family, human beta-defensin-1 (hBD-1) and -2 (hBD-2) that contribute to innate immune responses. The potential importance of these peptides in oral health and disease susceptibility is only recently beginning to be appreciated. Production of hBD-1 and hBD-2 is stimulated when HGECs are exposed to an oral commensal bacterium, Fusobacterium nucleatum. HBD-1 mRNA is also up regulated by exposure to TNFalpha, an inflammatory mediator, while hBD-1 mRNA is constitutively expressed. These preliminary studies suggest that commensal organisms may be important in maintaining the normal protective barrier function of the oral mucosa in vivo by partial activation of the innate immune system. Several findings or hypotheses are the focus of this project: 1) that expression of beta-defensins is associated with differentiation in oral mucosa; 2) that beta-defensins are regulated by known or novel cell surface receptors, possibly including CD14 and TLRs, 3) that signal transduction via the transcription factor NF kB is critical for hBD-2 mRNA expression, 4) that the pathway for stimulation may differ from that of other host innate immune responses, such as the chemokine IL-8, 5) that new gene expression may be required. The present proposal uses cell and molecular studies to investigate the regulation of expression of beta-defensins in relation to epithelial differentiation, and to identify cell surface receptors and signaling pathways responsible for their expression in response to the oral commensal organism, F. nucleatum. Understanding the signaling pathways and means to enhance peptide expression will have future potential for enhancing antimicrobial peptide expression for prevention and treatment of oral microbial disorders, including periodontal disease, caries, recurrent candidal infections, and oral mucositis.

描述（改编自申请人的摘要）：口腔上皮细胞作为 通过先天宿主防御保护口腔和牙周健康的第一道防线 机制。人牙龈上皮细胞（HGEC）表达两种抗菌剂 β-防御素家族肽、人 β-防御素-1 (hBD-1) 和 -2 (hBD-2) 有助于先天免疫反应。潜在的重要性 这些肽在口腔健康和疾病易感性方面的作用最近才被研究 开始受到赞赏。当以下情况时，会刺激 hBD-1 和 hBD-2 的产生： HGEC 暴露于口腔共生细菌，具核梭杆菌。 HBD-1 mRNA 也会因暴露于 TNFα（一种炎症物质）而上调。 介体，而 hBD-1 mRNA 则组成型表达。这些初步的 研究表明，共生生物可能对于维持 口腔粘膜在体内的正常保护屏障功能通过部分 激活先天免疫系统。一些发现或假设 该项目的重点：1）β-防御素的表达与 口腔粘膜分化； 2）β-防御素受已知的调节 或新的细胞表面受体，可能包括 CD14 和 TLR，3) 通过转录因子 NF kB 进行信号转导对于 hBD-2 至关重要 mRNA 表达，4) 刺激途径可能与 其他宿主先天免疫反应，例如趋化因子 IL-8，5) 可能需要基因表达。本提案使用细胞和分子 β-防御素表达调控的研究 与上皮分化的关系，并识别细胞表面受体 以及负责其表达以响应口腔的信号通路 共生生物，F. nucleatum。了解信号通路和 增强肽表达的方法将具有增强肽表达的未来潜力 抗菌肽表达用于预防和治疗口腔微生物 疾病，包括牙周病、龋齿、复发性念珠菌病 感染和口腔粘膜炎。