Molecular Basis of Bioelectronic Medicine

 描述（由申请方提供）：由对感染和无菌损伤的免疫应答介导的炎症是疾病的主要潜在原因。炎症分子机制的研究进展有望为严重脓毒症、休克、缺血再灌注损伤、自身免疫性疾病和其他具有国家重要性的衰弱性疾病开发未来的治疗方法。NIGMS在主要研究者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。这项工作现在已经发展到启动一个新的领域，称为“生物电子医学”，这有望成为使用电子设备开发针对抗炎神经回路的疗法的战略。本提案旨在了解PI实验室现有的三个RO1资助项目中有关控制炎症的分子机制的未回答问题。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。第三是了解在神经递质影响下调节细胞因子释放的分子机制，包括细胞因子基因表达和炎性小体活性的调节。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重要的新数据。

 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.