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

Abstract

Background: Urate through NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome-dependent caspase-1 activation stimulates macrophages to secrete inteleukin-1 beta (IL-1 beta). 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. Methods: 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-1 beta 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. Results: Urate induced caspase-1 activation and IL-1 beta release by T-cells. It also induced proliferation of T-cells. Glyburide inhibited urate-induced caspase-1 activation, IL-1 beta secretion and proliferation. Conclusions: Urate, a well defined danger signal, stimulates directly human T-cells in a NLRP3 infmmasomela-dependent way. The subsequent IL-1 beta secretion could enhance inflammation, whereas expansion of T-cell clones could facilitate a subsequent adaptive immune response.