Molecular Basis of Bioelectronic Medicine

 描述(申请人提供)：炎症，由对感染和无菌损伤的免疫反应调节，是疾病的主要潜在原因。了解炎症的分子机制的进展有望为未来开发严重脓毒症、休克、缺血再灌注损伤、自身免疫性疾病和其他国家重要的衰弱疾病的治疗方法。由NIGMS在首席研究员实验室支持的研究揭示了通过识别和靶向特定细胞因子，以及通过映射和靶向控制其活动的特定神经回路来控制炎症的机制。这项工作现在已经进展到启动一个新的领域，被称为“生物电子医学”，它有望成为开发使用电子设备靶向抗炎神经回路的治疗方法的战略。目前的提案试图了解关于控制炎症的分子机制的悬而未决的问题，这些问题来自于PI实验室现有的三个RO1资助的项目。首先是了解控制免疫反应的反射神经回路的身份和机制。第二是了解炎症的细胞因子介质的生物学，这些介质对于疾病的病因是必要的和充分的。三是了解神经递质影响下细胞因子释放的分子机制，包括细胞因子基因表达和炎症体活性的调节。这项工作的成功完成将为开发使用生物电子设备预防和治疗炎症的治疗方式提供必要的重要新数据。

 DESCRIPTION (provided by applicant): Inflammation, mediated by the immune response to infection and sterile injury, is a major underlying cause of disease. Advances in understanding the molecular mechanisms of inflammation hold promise for developing future therapies for severe sepsis, shock, ischemia reperfusion injury, autoimmune diseases, and other debilitating diseases of national importance. Research supported by the NIGMS in the principle investigator's lab has revealed mechanisms to control inflammation by identifying and targeting specific cytokines, and by mapping and targeting specific neural circuits that control their activity. This work has now progressed to launching a new field, termed "bioelectronic medicine," which holds promise as strategy to develop therapies using electronic devices to target anti-inflammatory neural circuits. The present proposal seeks to understand unanswered questions about the molecular mechanisms controlling inflammation as derived from three existing RO1 funded projects in the PI's laboratory. The first is to understand the identity and mechanisms of the reflex neural circuits that control immune responses. The second is to understand the biology of cytokine mediators of inflammation that are necessary and sufficient for disease causation. And the third is to understand the molecular mechanisms that regulate cytokine release under the influence of neurotransmitters, including regulation of cytokine gene expression and inflammasome activity. The successful completion of this work will provide significant new data necessary to develop therapeutic modalities for the prevention and treatment of inflammation using bioelectronic devices.