Figure 4

Nanoparticles induce mature IL-1β secretion through adenosine and P1 receptor signalling. LPS-primed murine BMDMs were stimulated for 6 h with nano-SiO₂ or nano-TiO₂ in the presence of increasing concentrations of apyrase grade VII (0.3, 1, 3 or 10 U/ml) (a). Nano-SiO₂- and nano-TiO₂-induced IL-1β were slightly decreased and then rapidly increased (a). LPS-primed BMDMs were also stimulated for 6 h with nano-SiO₂ or nano-TiO₂ in the presence of increasing doses of ADA (0.3, 1, 3 and 10 U/ml) (b). Apyrase grade VII or ADA alone had no effect on IL-1β secretion by murine macrophages (a,b). PMA-primed THP1 were stimulated for 6 h with nano-SiO₂ (250 μg/ml) in the presence of different concentrations of apyrase VII (c) or ADA (d). Nano-SiO₂-induced eATP decreased by increasing apyrase VII, whereas IL-1β remained elevated (c). ADA dose dependently decreased both nano-SiO₂-induced IL-1β and eATP secretions (d). Apyrase VII or ADA alone had no effect on IL-1β and eATP secretions by human macrophages (c,d). LPS-primed murine BMDMs were stimulated for 6 h with nano-SiO₂ or nano-TiO₂ in the presence of increasing concentrations of NECA (e) or AMP-CP (f). IL-1β secretion induced by nanoparticles was increased in the presence of NECA (e) and remained stable in the presence of AMP-CP (f). Data are representative of three independent experiments (*P≤0.05, **P≤0.01, ***P≤0.001, ns: not statistically different)