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TRPM 通道作为对抗炎症性疾病的潜在治疗靶点。

TRPM channels as potential therapeutic targets against pro-inflammatory diseases.

机构信息

Walther Straub Institute of Pharmacology and Toxicology, LMU Munich, Germany.

Walther Straub Institute of Pharmacology and Toxicology, LMU Munich, Germany.

出版信息

Cell Calcium. 2017 Nov;67:105-115. doi: 10.1016/j.ceca.2017.05.002. Epub 2017 May 3.

Abstract

The immune system protects our body against foreign pathogens. However, if it overshoots or turns against itself, pro-inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease, or diabetes develop. Ions, the most basic signaling molecules, shape intracellular signaling cascades resulting in immune cell activation and subsequent immune responses. Mutations in ion channels required for calcium signaling result in human immunodeficiencies and highlight those ion channels as valued targets for therapies against pro-inflammatory diseases. Signaling pathways regulated by melastatin-like transient receptor potential (TRPM) cation channels also play crucial roles in calcium signaling and leukocyte physiology, affecting phagocytosis, degranulation, chemokine and cytokine expression, chemotaxis and invasion, as well as lymphocyte development and proliferation. Therefore, this review discusses their regulation, possible interactions and whether they can be exploited as targets for therapeutic approaches to pro-inflammatory diseases.

摘要

免疫系统保护我们的身体免受外来病原体的侵害。然而,如果免疫系统反应过度或攻击自身,就会发展出炎症性疾病,如类风湿关节炎、炎症性肠病或糖尿病。离子是最基本的信号分子,它们塑造细胞内信号级联反应,导致免疫细胞激活和随后的免疫反应。钙信号所需的离子通道突变导致人类免疫缺陷,并强调这些离子通道是治疗炎症性疾病的有价值的靶点。由 melastatin 样瞬时受体电位 (TRPM) 阳离子通道调节的信号通路也在钙信号和白细胞生理学中发挥关键作用,影响吞噬作用、脱颗粒、趋化因子和细胞因子表达、趋化和侵袭以及淋巴细胞发育和增殖。因此,本文讨论了它们的调节、可能的相互作用以及它们是否可以作为炎症性疾病治疗方法的靶点。

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