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PMA Induces Vaccine Adjuvant Activity by the Modulation of TLR Signaling Pathway
Toll-like receptor (TLR) ligands are being developed for use as vaccine adjuvants and as immunomodulators because of their ability to stimulate innate and adaptive immune responses. Flagellin, a TLR5 ligand, was reported to show potent mucosal vaccine adjuvant activity. To identify ligands that pote...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Hindawi Publishing Corporation
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4052173/ https://www.ncbi.nlm.nih.gov/pubmed/24948847 http://dx.doi.org/10.1155/2014/406514 |
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author | Oh, Dool-Ri Kang, Hu Won Kim, Jong-Ro Kim, Sunoh Park, In-Kyu Rhee, Joon Haeng Oh, Won Keun Kim, Young Ran |
author_facet | Oh, Dool-Ri Kang, Hu Won Kim, Jong-Ro Kim, Sunoh Park, In-Kyu Rhee, Joon Haeng Oh, Won Keun Kim, Young Ran |
author_sort | Oh, Dool-Ri |
collection | PubMed |
description | Toll-like receptor (TLR) ligands are being developed for use as vaccine adjuvants and as immunomodulators because of their ability to stimulate innate and adaptive immune responses. Flagellin, a TLR5 ligand, was reported to show potent mucosal vaccine adjuvant activity. To identify ligands that potentiate the adjuvant activity of flagellin, we screened a plant library using HEK293T cells transiently cotransfected with phTLR5 and pNF-κB-SEAP plasmids. The 90% EtOH extract from Croton tiglium showed significant NF-κB transactivation in a TLR5-independent manner along with the increase of a flagellin activity. We have studied to characterize an active component from Croton tiglium and to elucidate the action mechanisms. Phorbol 12-myristate 13-acetate (PMA) was isolated as an active component of Croton tiglium by activity-guided fractionation, column chromatography, HPLC, NMR, and MS. PMA at a range of nM induced PKC-dependent NF-κB activation and IL-8 production in both TLR5− and TLR5+ assay systems. In in vivo mouse vaccination model, PMA induced antigen-specific IgG and IgA antibody responses and increased IL-12 production corresponding to T cell responses in spleen lymphocytes. These results suggest that PMA would serve as an efficacious mucosal vaccine adjuvant. |
format | Online Article Text |
id | pubmed-4052173 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-40521732014-06-19 PMA Induces Vaccine Adjuvant Activity by the Modulation of TLR Signaling Pathway Oh, Dool-Ri Kang, Hu Won Kim, Jong-Ro Kim, Sunoh Park, In-Kyu Rhee, Joon Haeng Oh, Won Keun Kim, Young Ran Mediators Inflamm Research Article Toll-like receptor (TLR) ligands are being developed for use as vaccine adjuvants and as immunomodulators because of their ability to stimulate innate and adaptive immune responses. Flagellin, a TLR5 ligand, was reported to show potent mucosal vaccine adjuvant activity. To identify ligands that potentiate the adjuvant activity of flagellin, we screened a plant library using HEK293T cells transiently cotransfected with phTLR5 and pNF-κB-SEAP plasmids. The 90% EtOH extract from Croton tiglium showed significant NF-κB transactivation in a TLR5-independent manner along with the increase of a flagellin activity. We have studied to characterize an active component from Croton tiglium and to elucidate the action mechanisms. Phorbol 12-myristate 13-acetate (PMA) was isolated as an active component of Croton tiglium by activity-guided fractionation, column chromatography, HPLC, NMR, and MS. PMA at a range of nM induced PKC-dependent NF-κB activation and IL-8 production in both TLR5− and TLR5+ assay systems. In in vivo mouse vaccination model, PMA induced antigen-specific IgG and IgA antibody responses and increased IL-12 production corresponding to T cell responses in spleen lymphocytes. These results suggest that PMA would serve as an efficacious mucosal vaccine adjuvant. Hindawi Publishing Corporation 2014 2014-05-18 /pmc/articles/PMC4052173/ /pubmed/24948847 http://dx.doi.org/10.1155/2014/406514 Text en Copyright © 2014 Dool-Ri Oh et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Oh, Dool-Ri Kang, Hu Won Kim, Jong-Ro Kim, Sunoh Park, In-Kyu Rhee, Joon Haeng Oh, Won Keun Kim, Young Ran PMA Induces Vaccine Adjuvant Activity by the Modulation of TLR Signaling Pathway |
title | PMA Induces Vaccine Adjuvant Activity by the Modulation of TLR Signaling Pathway |
title_full | PMA Induces Vaccine Adjuvant Activity by the Modulation of TLR Signaling Pathway |
title_fullStr | PMA Induces Vaccine Adjuvant Activity by the Modulation of TLR Signaling Pathway |
title_full_unstemmed | PMA Induces Vaccine Adjuvant Activity by the Modulation of TLR Signaling Pathway |
title_short | PMA Induces Vaccine Adjuvant Activity by the Modulation of TLR Signaling Pathway |
title_sort | pma induces vaccine adjuvant activity by the modulation of tlr signaling pathway |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4052173/ https://www.ncbi.nlm.nih.gov/pubmed/24948847 http://dx.doi.org/10.1155/2014/406514 |
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