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

虽然秋水仙碱作为痛风和家族性地中海热的一线治疗药物(1)，但先前的临床试验如COLTOT和LoDoCo显示，秋水仙碱治疗可显著降低冠心病患者心血管事件的风险（2,3）。然而，对诱导心血管疾病（CVD）保护特性的机制的认识尚未完全覆盖。在这个项目中，我们将绘制生长分化因子15 （GDF15）发挥的抗炎特性，GDF15是秋水仙碱治疗后分泌的一种肝因子。在小鼠骨髓细胞中，GDF15先前被证明可以抑制il -1 β的产生，重要的促炎细胞因子，以及细胞粘附和募集。(4、5)。我们将通过进一步研究GDF15和FGF1，潜在的结合伙伴，对促炎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因素。

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.