Protein-bound polysaccharide-K induces IL-1ß via TLR2 and NLRP3 inflammasome activation.
Innate Immun
; 20(8): 857-66, 2014 Nov.
Article
em En
| MEDLINE
| ID: mdl-24323452
ABSTRACT
Inflammasome activation has been shown to regulate both innate and adaptive immune responses. It is important to investigate whether immune-enhancing natural products can also activate inflammasome. The current study examined the potential of protein-bound polysaccharide-K (PSK), a hot water extract from Trametes versicolor, to activate inflammasome. Using THP-1 cells, we have demonstrated that PSK induces both pro-IL-1ß and mature IL-1ß in THP-1 cells in a caspase 1- and NLRP3-dependent manner. PSK also induces IL-1ß and IL-18 in human PBMC. Cathepsin B is required for PSK-induced inflammasome activation as CA-074-Me, a cathepsin B inhibitor, significantly decreased PSK-induced IL-1ß. PSK induces NLRP3 at both mRNA and protein level. Comparison of PSK-induced IL-1ß in bone marrow-derived macrophages from wild type C57BL/6 mice, TLR2(-/-), P2X7R(-/-) and NLRP3(-/-) mice demonstrated that PSK-induced IL-1ß is dependent on both TLR2 and NLRP3. P2X7R is not required for PSK-induced inflammasome activation, but enhances PSK-induced caspase-1 activation and IL-1ß induction. Altogether, these results demonstrated that PSK induces inflammasome activation and production of IL-1ß in a TLR2- and NLRP3-dependent mechanism. These results provide novel insights into the mechanisms of the immune modulatory effects of PSK.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteoglicanas
/
Proteínas de Transporte
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Receptor 2 Toll-Like
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Interleucina-1beta
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Inflamassomos
Limite:
Animals
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Humans
Idioma:
En
Revista:
Innate Immun
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
BACTERIOLOGIA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos