Capsular material of the opportunistic fungus Cryptococcus neoformans is mainly composed of a polysaccharide named glucuronoxylomannan (GXM). In this study, the effects of GXM were analyzed in an in vivo experimental system of LPS-induced shock. Endotoxic shock was induced in mice by a single intraperitoneal injection of LPS from Escherichia coli. GXM treatment reduced the mortality of mice at early stages. Mice treated with LPS alone showed markedly increased plasma levels of TNF-α, IL-1β, and IL-6, whereas mice treated with GXM too showed significantly lower plasma levels of these cytokines. This effect was related to a marked suppression of Akt and IkBα activation. Importantly, the inhibitory effect of GXM on pro-inflammatory cytokine secretion was reproduced by treatment with Wortmannin, an inhibitor of the Akt transcription pathway. Our results indicate that GXM has a beneficial effect on endotoxic shock, resulting in a significant increase in rate of survival by dampening the hyper-inflammatory response.

A Purified Capsular Polysaccharide Markedly Inhibits Inflammatory Response during Endotoxic Shock.

PICCIONI, MIRANDA;MONARI, Claudia;PERICOLINI, Eva;GABRIELLI, ELENA;PIETRELLA, Donatella;PERITO, Stefano;BISTONI, Francesco;VECCHIARELLI, Anna
2013

Abstract

Capsular material of the opportunistic fungus Cryptococcus neoformans is mainly composed of a polysaccharide named glucuronoxylomannan (GXM). In this study, the effects of GXM were analyzed in an in vivo experimental system of LPS-induced shock. Endotoxic shock was induced in mice by a single intraperitoneal injection of LPS from Escherichia coli. GXM treatment reduced the mortality of mice at early stages. Mice treated with LPS alone showed markedly increased plasma levels of TNF-α, IL-1β, and IL-6, whereas mice treated with GXM too showed significantly lower plasma levels of these cytokines. This effect was related to a marked suppression of Akt and IkBα activation. Importantly, the inhibitory effect of GXM on pro-inflammatory cytokine secretion was reproduced by treatment with Wortmannin, an inhibitor of the Akt transcription pathway. Our results indicate that GXM has a beneficial effect on endotoxic shock, resulting in a significant increase in rate of survival by dampening the hyper-inflammatory response.
2013
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11391/1009068
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