Format

Send to

Choose Destination
Innate Immun. 2014 Nov;20(8):857-66. doi: 10.1177/1753425913513814. Epub 2013 Dec 9.

Protein-bound polysaccharide-K induces IL-1β via TLR2 and NLRP3 inflammasome activation.

Author information

1
Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington, Seattle, WA, USA.
2
Bastyr University, Kenmore, WA, USA.
3
National Center for Natural Products Research, University of Mississippi, University, MS, USA.
4
Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington, Seattle, WA, USA hlu@u.washington.edu.

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-1β and mature IL-1β in THP-1 cells in a caspase 1- and NLRP3-dependent manner. PSK also induces IL-1β 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-1β. PSK induces NLRP3 at both mRNA and protein level. Comparison of PSK-induced IL-1β in bone marrow-derived macrophages from wild type C57BL/6 mice, TLR2(-/-), P2X7R(-/-) and NLRP3(-/-) mice demonstrated that PSK-induced IL-1β 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-1β induction. Altogether, these results demonstrated that PSK induces inflammasome activation and production of IL-1β in a TLR2- and NLRP3-dependent mechanism. These results provide novel insights into the mechanisms of the immune modulatory effects of PSK.

KEYWORDS:

NLRP3 inflammasome; PSK; TLR2

PMID:
24323452
PMCID:
PMC4414124
DOI:
10.1177/1753425913513814
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center