Malarial Hemozoin Activates the NLRP3 Inflammasome through Lyn and Syk Kinases
Figure 1
Hemozoin induces IL-1β maturation and secretion and is dependent on HSP-90 stability and caspase-1 activation.
(A) PMA-differentiated THP-1 cells (0.75×106 cells/0.5 mL) were stimulated with the indicated concentration of hemozoin (Hz) or Monosodium Urate (MSU) and (B) pre-treated or not with the HSP-90 inhibitor geldanamycin D or (C) the caspase-1 specific inhibitor Y-VAD-FMK or the broad caspase inhibitor Z-VAD-CHO. (D) Bone marrow derived macrophages – BMDM - (1.5×106/mL) from either caspase-1-deficient or wild type (WT) mice were pre-treated with LPS (100 ng/mL) for three hours, washed and incubated with Hz (200 µg/mL) or MSU (100 µg/mL). After six hours of incubation, supernatant (SN) and cell extracts were collected and subjected to Western blot analysis with the indicated antibodies. Data show one experiment representative of three to five independent experiments.