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PMA Induces Vaccine Adjuvant Activity by the Modulation of TLR Signaling Pathway
- Source :
- Mediators of Inflammation, Vol 2014 (2014)
- Publication Year :
- 2014
- Publisher :
- Hindawi Limited, 2014.
-
Abstract
- 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.
Details
- Language :
- English
- ISSN :
- 09629351 and 14661861
- Volume :
- 2014
- Database :
- Directory of Open Access Journals
- Journal :
- Mediators of Inflammation
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.33177b69bb6e4e4c9971e54fd8713d85
- Document Type :
- article
- Full Text :
- https://doi.org/10.1155/2014/406514