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• W2138177598 abstract "ABSTRACT Pneumolysin is a pore-forming cytolysin known as a major virulence determinant of Streptococcus pneumoniae . This protein toxin has also been shown to activate the Toll-like receptor 4 (TLR4) signaling pathway. In this study, a mutant S. pneumoniae strain deficient in pneumolysin (Δ ply ) and a recombinant pneumolysin protein (rPLY) were constructed. Upon infection of macrophages in vitro, the ability to induce the production of interleukin-1α (IL-1α), IL-1β, and IL-18 was severely impaired in the Δ ply mutant, whereas there was no marked difference in the induction of tumor necrosis factor alpha (TNF-α) and IL-12p40 between the wild type and the Δ ply mutant of S. pneumoniae . When macrophages were stimulated with rPLY, the production of IL-1α, IL-1β, and IL-18 was strongly induced in a TLR4-dependent manner, whereas lipopolysaccharide, a canonical TLR4 agonist, hardly induced these cytokines. In contrast, lipopolysaccharide was more potent than rPLY in inducing the production of TNF-α, IL-6, and IL-12p40, the cytokines requiring no caspase activation. Activation of caspase-1 was observed in macrophages stimulated with rPLY but not in those stimulated with lipopolysaccharide, and the level of activation was higher in macrophages infected with wild-type S. pneumoniae than in those infected with the Δ ply mutant. These results clearly indicate that pneumolysin plays a key role in the host response to S. pneumoniae , particularly in the induction of caspase-1-dependent cytokines." @default.
• W2138177598 created "2016-06-24" @default.
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• W2138177598 date "2008-04-01" @default.
• W2138177598 modified "2023-10-04" @default.
• W2138177598 title "Critical Involvement of Pneumolysin in Production of Interleukin-1α and Caspase-1-Dependent Cytokines in Infection with<i>Streptococcus pneumoniae</i>In Vitro: a Novel Function of Pneumolysin in Caspase-1 Activation" @default.
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• W2138177598 doi "https://doi.org/10.1128/iai.01269-07" @default.
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