Uric acid induces caspase-1 activation, IL-1β secretion and P2X7 receptor dependent proliferation in primary human lymphocytes
AuthorEleftheriadis, T.; Pissas, G.; Karioti, A.; Antoniadi, G.; Golfinopoulos, S.; Liakopoulos, V.; Mamara, A. M.; Speletas, M.; Koukoulis, G.; Stefanidis, I.
Background: Urate through Nacht Domain, Leucine-Rich Repeat, and pyrin domain-containing protein 3 (NALP3) dependent caspase-1 activation stimulates macrophages to secrete inteleukin-1β (IL-1β). Purinergic receptor P2X7 plays a role in the urate induced NALP3 activation. Urate also enhances adaptive immunity indirectly through its effect on antigen presenting cells. In this study, the direct effect of urate on primary human lymphocytes was evaluated. Methods: Lymphocytes were cultured with or without monosodium urate crystals in the presence or not of a P2X7 inhibitor. Caspase-1 activity was assessed colorimetrically in cell lysates and IL-1β was measured in supernatants with ELISA. Whole lymphocyte viability and proliferation, as well as T-cell proliferation were assessed by means of 2, 3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay and of flow cytometry respectively. Results: Urate induced caspase-1 activation and IL-1β release by lymphocytes. It also induced proliferation of whole lymphocytes and T-cells as well. P2X7 inhibitor abrogated lymphocyte proliferation. Conclusions: Urate, a well defined danger signal, stimulates directly human lymphocytes in a P2X7 dependent way. The subsequent IL-1β secretion could enhance inflammation, whereas expansion of lymphocyte clones could facilitate a subsequent adaptive immune response.
Showing items related by title, author, creator and subject.
Makris, D.; Lazarou, S.; Alexandrakis, M.; Kourelis, T. V.; Tzanakis, N.; Kyriakou, D.; Gourgoulianis, K. I. (2008)Background: T lymphocytes and especially the subpopulations of CD8+ cells are believed to have a key role in COPD pathophysiology, but there are only few data regarding the role of these cells in COPD exacerbation. Aim: ...
Dichloroacetate at therapeutic concentration alters glucose metabolism and induces regulatory t-cell differentiation in alloreactive human lymphocytes Eleftheriadis, T.; Pissas, G.; Karioti, A.; Antoniadi, G.; Antoniadis, N.; Liakopoulos, V.; Stefanidis, I. (2013)Background: Most cancer cells rely on aerobic glycolysis. Dichloroacetate (DCA) inhibits aerobic glycolysis and is a promising relatively nontoxic anticancer compound. However, rapidly proliferating effector T-cells also ...
Decreased Expression of the CD3ζ Chain in T Cells Infiltrating the Synovial Membrane of Patients with Osteoarthritis Sakkas, L. I.; Koussidis, G.; Avgerinos, E.; Gaughan, J.; Platsoucas, C. D. (2004)Osteoarthritis (OA) is a heterogeneous disease which rheumatologists consider to be noninflammatory. However, recent studies suggest that, at least in certain patients, OA is an inflammatory disease and that patients often ...