ABSTRACT
Aim To explore the influences of scutellarin on ATP-induced NLRP3 inflammasome activation and pyroptosis,using LPS-primed murine macrophages J774A.1 as an inflammatory cell model,and to explore the underlying mechanism.Methods The effects of scutellarin on ATP-induced pyroptosis in murine J774A.1 macrophages were analyzed by propidium iodide (PI) staining assay.The levels of IL-1β,caspase-1 and HMGB1 in cell lysates and culture supernatants were analysed using Western blot.The levels of IL-1β in cell culture supernatants were measured by cytometric beads array (CBA).Results ATP significantly induced caspase-1 activation and mature IL-1β and HMGB1 release into the culture supernatants in LPS-primed murine J774A.1 macrophages,and induced pyroptosis.Scutellarin treatment dose-dependently inhibited ATP-induced caspase-1 activation,mature IL-1β and HMGB1 release,and pyroptosis.Notably,scutellarin's inhibitory effects on ATP-induced pyroptosis were markedly reversed by the adenylate cyclase inhibitor MDL12330A and selective protein kinase A (PKA) inhibitor H89.Conclusion Scutellarin inhibits NLRP3 inflammasome activation and pyroptosis by modulating the PKA activity in macrophages,thereby exhibiting anti-inflammatory activities.
ABSTRACT
The study was aimed to investigate the mechanism of cytotoxic effect of trichosanthin (TCS) on leukemia or lymphoma cell lines. Trypan blue exclusion was used to measure the effect of TCS on cell growth and flow cytometry was used to detect the effects of TCS on cell apoptosis and cell cycle. The results indicated that the TCS could inhibit proliferation of various leukemia/lymphoma cell lines at 12.5 microg/ml concentration, but the effect of TCS on T-lymphocyte and macrophage cell lines showed inducing cell apoptosis and the effect of TCS on B lymphocyte cell line showed inhibiting cell growth. Detection of the cell cycle revealed that TCS could arrest B lymphocytes at S phase, but not had this effect on T lymphocytes at the same condition. It is concluded that TCS can kill leukemia/lymphoma cells through different mechanisms such as inducing cell apoptosis or arresting cell cycle according to cell types.