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Mediators of Inflammation
Volume 2014 (2014), Article ID 406514, 8 pages
http://dx.doi.org/10.1155/2014/406514
Research Article

PMA Induces Vaccine Adjuvant Activity by the Modulation of TLR Signaling Pathway

1Jeollanamdo Institute of Natural Resources Research, Jangheung, Jeollanamdo 529-851, Republic of Korea
2Korea INSPharm Inc. 1065, Dong-myeon, Hwasun, Jeollanamdo 519-882, Republic of Korea
3Department of Biomedical Science and BK21 PLUS Center for Creative Biomedical Scientists, Chonnam National University Medical School, Gwangju 501-757, Republic of Korea
4Clinical Vaccine R&D Center, Chonnam National University Medical School, Gwangju 501-757, Republic of Korea
5Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea
6Department of Pharmaceutical Engineering, Dongshin University, Naju, Jeollanamdo 520-724, Republic of Korea

Received 4 January 2014; Revised 31 March 2014; Accepted 1 April 2014; Published 18 May 2014

Academic Editor: Seong-Gyu Ko

Copyright © 2014 Dool-Ri Oh et al. 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.

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.