译者:张文静 校对:马丹 审核:张莉芸
Abstract :-IVES: To investigate the effects and mechanisms of action of high-density lipoproteins (HDL) in monosodium urate (MSU) crystal-induced inflammation -that is, gouty inflammation, in vivo.METHODS: Air pouches raised on the backs of mice were injected with MSU crystals or tumour necrosis factor (TNF) in the presence or absence of HDL and/or interleukin (IL)-1 receptor antagonist (IL-1Ra) for 3 h. Leucocyte count and neutrophil percentage in pouch fluids were measured using a haemocytometer and May-Grünwald-Giemsa staining. The cytokine production and - in the pouch were measured by ELISA and quantitative RT-PCR.RESULTS: MSU crystals induced leucocyte infiltration, mostly neutrophils, and the release of IL-1β, IL-6, chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine (C-C motif) ligand 2 (CCL2) and IL1Ra in pouch fluids. TNF remained under the detection limit. MSU crystals triggered IL-1β, IL- 6 and CXCL1 - in both pouch exudates and membranes, whereas CCL2 and TNF mRNA were not modulated. The co-injection of MSU crystals and HDL inhibited leucocyte influx by 59% and neutrophil infiltration by 83% and, in turn, both protein and mRNA levels of all assessed proinflammatory cytokines were reduced, but not those of IL-1Ra. Similar results were obtained when mice were injected with MSU crystals pretreated with HDL or TNF instead of crystals. When HDL and IL-1Ra were added together they displayed additional inhibition, suggesting different mechanisms of action.CONCLUSIONS: This study demonstrated that HDL may represent an important factor in the modulation of gouty inflammation by acting on both tissue and infiltrating cells -that is, synovial tissue and synovial fluid cells. HDL display anti-inflammatory activity, in part, by interacting with crystals but also by directly acting on cells.
摘要 目的:探讨高密度脂蛋白(HDL)对单钠尿酸盐结晶(MSU)诱导的痛风性炎症的影响及其作用机制。方法:在小鼠背部制造气囊模型,向气囊内注射MSU结晶或肿瘤坏死因子(TNF),同时加入或不加入HDL和/或白介素1受体拮抗剂(IL-1Ra),共作用3小时。应用血细胞计数器和May-Grünwald-Giemsa染色法检测气囊中白细胞数量和中性粒细胞比例。应用ELISA法和定量RT-PCR法检测细胞因子的产生和表达情况。结果:MSU晶体可诱导白细胞浸润,尤其是中性粒细胞浸润,其可释放 IL-1β, IL-6, 趋化因子 (C-X-C motif)配体1 (CXCL1), 趋化因子(C-C motif)配体 2 (CCL2) 和 IL-1Ra。而注射TNF时上述各指标低于检测值。MSU晶体促进气囊渗出液和气囊膜中IL-1β, IL-6 和CXCL1表达,而CCL2 和 TNF mRNA 水平无变化。同时注射MSU晶体和HDL可以抑制59%的白细胞浸润,抑制83%的中性粒细胞浸润,所有促炎因子的蛋白质和mRNA水平均下调,而同时注射IL-1Ra则无此作用。小鼠在经HDL预处理之后再给予MSU结晶或给予TNF可得到相似的结果。当同时给予HDL和IL-1Ra时,表现出额外的抑制作用,提示他们的作用机制不同。结论:本研究表明HDL可能通过作用于组织和浸润细胞-即滑膜组织和滑液细胞,进而调控痛风性炎症。HDL通过与结晶体相互作用,也通过直接作用于细胞而发挥抗炎作用。
引自:Scanu A, Luisetto R, Oliviero F, et al. High-density lipoproteins inhibit urate crystal-induced inflammation in mice. Ann Rheum Dis. 2013 Dec 10. doi: 10.1136/annrheumdis-2013-203803.