Mechanism of the anti-inflammatory effect exerted by colchicine on pro-inflammatory macrophages and neutrophils

秋水仙碱对促炎巨噬细胞和中性粒细胞的抗炎作用机制

• 批准号: 2461305
• 金额: --
• 依托单位: University of Dundee
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2461305
• 关键词: Mechanism; anti; inflammatory; effect; exerted

Although colchicine serves as a first-line treatment of gout and familial Mediterranean fever (1), previous clinical trials such as COLTOT and LoDoCo showed that colchicine treatment significantly reduces risk of cardiovascular events in coronary heart disease patients (2, 3). However, the understanding to the mechanisms inducing cardiovascular disease (CVD) protective properties is yet to be fully covered.In this project, we will map on the anti-inflammatory properties exerted by growth differentiation factor 15 (GDF15), a hepatokine secreted post-colchicine treatment. In murine myeloid cells, GDF15 was previously shown to suppress IL-1beta production, important pro-inflammatory cytokine, and cell adhesion and recruitment. (4, 5). We will expand on these findings by further investigation of the GDF15 and FGF1, potential binding partner, effects on cytokine production, marker expression, metabolic profile and phagocytosis in pro-inflammatory macrophages and neutrophils as they are major contributors to progression of CVD, type II diabetes or autoimmune diseases.

尽管秋水仙碱是痛风和家族性地中海热的一线治疗药物（1），但COLTOT和LoDoCo等先前的临床试验表明，秋水仙碱治疗可显着降低冠心病患者发生心血管事件的风险（2，3）。然而，诱导心血管疾病（CVD）保护特性的机制尚未完全覆盖。在这个项目中，我们将绘制由生长分化因子15（GDF 15），秋水仙素治疗后分泌的肝细胞因子发挥的抗炎特性。在鼠骨髓细胞中，GDF 15先前显示抑制IL-1 β产生、重要的促炎细胞因子以及细胞粘附和募集。〔四、五〕。我们将通过进一步研究GDF 15和FGF 1，潜在的结合伴侣，对促炎性巨噬细胞和中性粒细胞中细胞因子产生，标志物表达，代谢特征和吞噬作用的影响来扩展这些发现，因为它们是CVD，II型糖尿病或自身免疫性疾病进展的主要贡献者。