Rheumatology Unit, Department of Medicine-DIMED, University of Padova, Padova, Italy.
Center of Experimental Surgery, University of Padova, Padova, Italy.
Ann Rheum Dis. 2015 Mar;74(3):587-94. doi: 10.1136/annrheumdis-2013-203803. Epub 2013 Dec 10.
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.
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 expression in the pouch were measured by ELISA and quantitative RT-PCR.
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 IL-1Ra in pouch fluids. TNF remained under the detection limit. MSU crystals triggered IL-1β, IL-6 and CXCL1 expression 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.
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.
研究高密度脂蛋白（HDL）在单钠尿酸盐（MSU）晶体诱导的炎症（即痛风性炎症）中的作用及其机制。
在背部气囊中注射 MSU 晶体或肿瘤坏死因子（TNF），同时存在或不存在 HDL 和/或白细胞介素（IL）-1 受体拮抗剂（IL-1Ra）3 小时。用血细胞计数器和迈-格努姆染色法测量囊液中的白细胞计数和中性粒细胞百分比。通过 ELISA 和定量 RT-PCR 测量囊液中的细胞因子产生和表达。
MSU 晶体诱导白细胞浸润，主要是中性粒细胞，并释放白细胞介素（IL）-1β、IL-6、趋化因子（C-X-C 基序）配体 1（CXCL1）、趋化因子（C-C 基序）配体 2（CCL2）和 IL-1Ra。TNF 仍低于检测限。MSU 晶体触发了 IL-1β、IL-6 和 CXCL1 在囊液和囊膜中的表达，而 CCL2 和 TNF mRNA 没有调节。MSU 晶体与 HDL 共同注射可使白细胞流入减少 59%，中性粒细胞浸润减少 83%，进而所有评估的促炎细胞因子的蛋白和 mRNA 水平均降低，但 IL-1Ra 除外。当用 HDL 预处理的 MSU 晶体或 TNF 代替晶体注射到小鼠中时，得到了相似的结果。当 HDL 和 IL-1Ra 一起添加时，它们显示出额外的抑制作用，表明它们的作用机制不同。
本研究表明，HDL 可能通过作用于组织和浸润细胞（即滑膜组织和滑膜液细胞）来调节痛风性炎症，这是一个重要的因素。HDL 通过与晶体相互作用以及直接作用于细胞来发挥抗炎活性。
