Inhibition of lipopolysaccharide (LPS) or toxin B signaling pathway limits the synergistic increase in interleukin 1β (IL-1β) production. IL-1β levels following the incubation of colistin (A) or TAK-242 (B) with the combination of Escherichia coli LPS (1 ng/mL) and toxin B (50 ng/mL). Both compounds interfere with LPS signaling and produced a dose-dependent reduction in IL-1β levels. IL-1β levels following the incubation of polyclonal antitoxin B antibody (C) at a concentration of 5 μg/mL with LPS (1 ng/mL) and different concentrations of toxin B. A similar reduction in IL-1β levels was observed with the NLPR3 inhibitor MCC 950 (D). For these experiments, a concentration of E. coli LPS of 1 ng/mL was used with various concentrations of toxin B. The concentration of MCC 950 was 1 μM for all toxin concentrations (white bars), though at the highest toxin concentration, a higher dose (10 µM, gray bar) was also studied. *P < .05. For all experiments, comparisons were done relative to no inhibitor added.
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