Azevedo M L V, Bonan N B, Dias G, Brehm F, Steiner T M, Souza W M, Stinghen A E M, Barreto F C, Elifio-Esposito Selene, Pecoits-Filho R, Moreno-Amaral A N
Pontifícia Universidade Católica do Paraná, PUCPR, Brazil.
Laboratory of Bacteriology, Department of Clinical Analysis, UFPR, Brazil.
Toxicol Lett. 2016 Nov 30;263:1-5. doi: 10.1016/j.toxlet.2016.10.006. Epub 2016 Oct 17.
Immune system dysfunction is a common condition in chronic kidney disease (CKD). The present study investigated the effect of p-Cresyl sulfate (pCS) on human cell line U937 monocyte-derived macrophages (MDM) activity. MDM (1×10 cells/mL) were incubated with pCS (10, 25, or 50μg/mL), with or without lipopolysaccharide (LPS; 25ng/mL) and then evaluated NO production, phagocytosis and antigen-presenting molecules expression (HLA-ABC, HLA-DR, CD80 and CD86). All analyses were performed by flow cytometry. All pCS concentrations were able to increase NO production (49±12.1%, 39.8±7.75%, 43.7±11.9%, respectively) compared to untreated cells (4.35±3.34%) after 6h incubation but only the lowest concentration increased this production after 12h (82.9±8.6%, 61±7.2%, 40.8±11.7%). Combined with LPS, the same results were observed. Regarding to phagocytosis, all concentrations were able to induce bead engulfment (35.4±2.71%, 30±3.04%, 23.28±4.58%). In addition, pCS (50μg/mL) was able to increase HLA-ABC and CD80 expression, showed a slight effect on HLA-DR expression and, no difference in basal CD86 levels. pCS can induce an increased oxidative burst and phagocytosis by human macrophages while no modulation of HLA-DR or CD86 expression was induced. Together, these results suggest that pCS induces macrophage activation but interfere in antigen processing, leading to a failure in adaptive immune response in CKD.
免疫系统功能障碍是慢性肾脏病（CKD）中的常见情况。本研究调查了对甲酚硫酸盐（pCS）对人细胞系U937单核细胞衍生巨噬细胞（MDM）活性的影响。将MDM（1×10个细胞/ mL）与pCS（10、25或50μg/ mL）一起孵育，添加或不添加脂多糖（LPS；25ng / mL），然后评估一氧化氮（NO）产生、吞噬作用和抗原呈递分子表达（HLA - ABC、HLA - DR、CD80和CD86）。所有分析均通过流式细胞术进行。与未处理的细胞（4.35±3.34%）相比，孵育6小时后，所有pCS浓度均能够增加NO产生（分别为49±12.1%、39.8±7.75%、43.7±11.9%），但仅最低浓度在12小时后增加了这种产生（82.9±8.6%、61±7.2%、40.8±11.7%）。与LPS联合使用时，观察到相同结果。关于吞噬作用，所有浓度均能够诱导珠子吞噬（35.4±2.71%、30±3.04%、23.28±4.58%）。此外，pCS（50μg/ mL）能够增加HLA - ABC和CD80表达，对HLA - DR表达有轻微影响，并且基础CD86水平无差异。pCS可诱导人巨噬细胞氧化爆发和吞噬作用增加，同时未诱导HLA - DR或CD86表达的调节。总之，这些结果表明pCS诱导巨噬细胞活化，但干扰抗原加工，导致CKD中适应性免疫反应失败。
