Urate crystals induce NLRP3 inflammasome-dependent IL-1β secretion and proliferation in isolated primary human T-cells

• Published in: Hippokratia Vol. 19; no. 1; pp. 41 - 46
• Main Authors: Eleftheriadis, T, Pissas, G, Antoniadi, G, Makri, P, Liakopoulos, V, Stefanidis, I
• Format: Journal Article
• Language: English
• Published: Greece SOCIETY OF "FRIENDS OF HIPPOKRATIA JOURNAL" 01.01.2015
• Subjects: Original; T-cells; NLRP3; caspase-1; Urate; inflammasome; interleukin-1β
• ISSN: 1108-4189; 1790-8019

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.