Eleftheriadis T, Pissas G, Antoniadi G, Makri P, Liakopoulos V, Stefanidis I
Department of Nephrology, Medical School, University of Thessaly, Larissa, Greece.
Hippokratia. 2015 Jan-Mar;19(1):41-6.
Urate through NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome-dependent caspase-1 activation stimulates macrophages to secrete inteleukin-1β (IL-1β). Urate also enhances adaptive immunity indirectly through its effect on antigen presenting cells. In this study, the direct effect of urate on isolated primary human T-cells was evaluated.
Isolated T-cells were cultured with or without monosodium urate crystals in the presence or not of the NLRP3 inflammasome inhibitor glyburide. Activated cleaved caspase-1 was assessed by means of western blotting, whereas caspase-1 activity was measured colorimetrically in the cell lysates. IL-1β was measured in the supernatants by means of enzyme-linked immunosorbent assay. T-cell proliferation was assessed by means of bromodeoxyuridine labelling and immunoenzymatic detection.
Urate induced caspase-1 activation and IL-1β release by T-cells. It also induced proliferation of T-cells. Glyburide inhibited urate-induced caspase-1 activation, IL-1β secretion and proliferation.
Urate, a well defined danger signal, stimulates directly human T-cells in a NLRP3 infmmasomela-dependent way. The subsequent IL-1β secretion could enhance inflammation, whereas expansion of T-cell clones could facilitate a subsequent adaptive immune response. Hippokratia 2015, 19 (1): 41-46.
尿酸通过含NOD样受体家族吡咯结构域蛋白3（NLRP3）炎性小体依赖的半胱天冬酶-1激活，刺激巨噬细胞分泌白细胞介素-1β（IL-1β）。尿酸还通过其对抗抗原呈递细胞的作用间接增强适应性免疫。在本研究中，评估了尿酸对分离的原代人T细胞的直接作用。
分离的T细胞在有或无尿酸钠晶体存在的情况下，在有或无NLRP3炎性小体抑制剂格列本脲的情况下进行培养。通过蛋白质印迹法评估活化的裂解半胱天冬酶-1，而在细胞裂解物中通过比色法测量半胱天冬酶-1活性。通过酶联免疫吸附测定法测量上清液中的IL-1β。通过溴脱氧尿苷标记和免疫酶检测评估T细胞增殖。
尿酸诱导T细胞半胱天冬酶-1激活和IL-1β释放。它还诱导T细胞增殖。格列本脲抑制尿酸诱导的半胱天冬酶-1激活、IL-1β分泌和增殖。
尿酸是一种明确的危险信号，以NLRP3炎性小体依赖的方式直接刺激人T细胞。随后的IL-1β分泌可增强炎症，而T细胞克隆的扩增可促进随后的适应性免疫反应。《希波克拉底》2015年，第19卷（1）：41 - 46页。
