| (1,3)-beta-glucans activate both dectin-1 and NLRP3 inflammasome in human macrophages. | |
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MedLine Citation:
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PMID: 20421639 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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beta-Glucans are naturally occurring polysaccharides that are the major cell wall components of fungi. Recognition of beta-glucans is mediated through a membrane-bound pattern recognition receptor called dectin-1, and gene knock-out studies have shown that dectin-1 plays an important role in antifungal immune response in vivo. In this report, we have studied the effect of large particulate (1,3)-beta-glucans, including curdlan, glucan from baker's yeast, paramylon, and zymosan, on inflammatory response in human macrophages. We show that beta-glucans activate the transcription of the proinflammatory cytokine IL-1beta through a dectin-1-dependent pathway in human macrophages. Moreover, dectin-1 receptor associated Syk tyrosine kinase was essential for beta-glucan induced IL-1beta mRNA expression. In contrast to LPS, beta-glucans also strongly activated the secretion of IL-1beta. This beta-glucan triggered IL-1beta release was abolished by cytochalasin D, an inhibitor of phagocytosis, demonstrating that cytosolic recognition of beta-glucans is required for IL-1beta response in human macrophages. RNA interference-mediated gene knockdown experiments demonstrated that cytoplasmic NLRP3 inflammasome is essential for beta-glucan-induced IL-1beta secretion. Moreover, our results suggest that beta-glucan-induced NLRP3 inflammasome activation is dependent on the dectin-1/Syk signaling pathway. Furthermore, our results suggest that the lysosomal cathepsin B protease, the formation of reactive oxygen species, and the efflux of potassium are needed for beta-glucan-induced NLRP3 inflammasome activation. In conclusion, our results show that beta-glucans are recognized by membrane-associated dectin-1 and cytoplasmic NLRP3 inflammasome resulting in IL-1beta gene transcription and IL-1beta secretion in human macrophages, respectively. |
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Authors:
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P?ivi Kankkunen; Laura Teiril?; Johanna Rintahaka; Harri Alenius; Henrik Wolff; Sampsa Matikainen |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-04-26 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 184 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-20 Completed Date: 2010-06-14 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 6335-42 Citation Subset: AIM; IM |
Affiliation:
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Unit of Excellence for Immunotoxicology, Finnish Institute of Occupational Health, Helsinki, Finland. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Blotting, Western Carrier Proteins / immunology*, metabolism Enzyme-Linked Immunosorbent Assay Fungal Proteins / immunology, metabolism Gene Expression Gene Expression Regulation / immunology Humans Interleukin-1beta / biosynthesis, immunology Macrophage Activation / immunology* Macrophages / immunology*, metabolism Membrane Proteins / immunology*, metabolism Nerve Tissue Proteins / immunology*, metabolism RNA Interference Reverse Transcriptase Polymerase Chain Reaction Signal Transduction / immunology beta-Glucans / immunology*, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Carrier Proteins; 0/Fungal Proteins; 0/Interleukin-1beta; 0/Membrane Proteins; 0/NLRP3 protein, human; 0/Nerve Tissue Proteins; 0/beta-Glucans; 0/dectin 1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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