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...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2014-01-01
|
| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2014/406514 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832558303525208064 |
|---|---|
| author | Dool-Ri Oh Hu Won Kang Jong-Ro Kim Sunoh Kim In-Kyu Park Joon Haeng Rhee Won Keun Oh Young Ran Kim |
| author_facet | Dool-Ri Oh Hu Won Kang Jong-Ro Kim Sunoh Kim In-Kyu Park Joon Haeng Rhee Won Keun Oh Young Ran Kim |
| author_sort | Dool-Ri Oh |
| collection | DOAJ |
| 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 | Article |
| id | doaj-art-33177b69bb6e4e4c9971e54fd8713d85 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-33177b69bb6e4e4c9971e54fd8713d852025-02-03T01:32:41ZengWileyMediators of Inflammation0962-93511466-18612014-01-01201410.1155/2014/406514406514PMA Induces Vaccine Adjuvant Activity by the Modulation of TLR Signaling PathwayDool-Ri Oh0Hu Won Kang1Jong-Ro Kim2Sunoh Kim3In-Kyu Park4Joon Haeng Rhee5Won Keun Oh6Young Ran Kim7Jeollanamdo Institute of Natural Resources Research, Jangheung, Jeollanamdo 529-851, Republic of KoreaJeollanamdo Institute of Natural Resources Research, Jangheung, Jeollanamdo 529-851, Republic of KoreaKorea INSPharm Inc. 1065, Dong-myeon, Hwasun, Jeollanamdo 519-882, Republic of KoreaJeollanamdo Institute of Natural Resources Research, Jangheung, Jeollanamdo 529-851, Republic of KoreaDepartment of Biomedical Science and BK21 PLUS Center for Creative Biomedical Scientists, Chonnam National University Medical School, Gwangju 501-757, Republic of KoreaClinical Vaccine R&D Center, Chonnam National University Medical School, Gwangju 501-757, Republic of KoreaKorea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of KoreaDepartment of Pharmaceutical Engineering, Dongshin University, Naju, Jeollanamdo 520-724, Republic of KoreaToll-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.http://dx.doi.org/10.1155/2014/406514 |
| spellingShingle | Dool-Ri Oh Hu Won Kang Jong-Ro Kim Sunoh Kim In-Kyu Park Joon Haeng Rhee Won Keun Oh Young Ran Kim PMA Induces Vaccine Adjuvant Activity by the Modulation of TLR Signaling Pathway Mediators of Inflammation |
| 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 |
| url | http://dx.doi.org/10.1155/2014/406514 |
| work_keys_str_mv | AT doolrioh pmainducesvaccineadjuvantactivitybythemodulationoftlrsignalingpathway AT huwonkang pmainducesvaccineadjuvantactivitybythemodulationoftlrsignalingpathway AT jongrokim pmainducesvaccineadjuvantactivitybythemodulationoftlrsignalingpathway AT sunohkim pmainducesvaccineadjuvantactivitybythemodulationoftlrsignalingpathway AT inkyupark pmainducesvaccineadjuvantactivitybythemodulationoftlrsignalingpathway AT joonhaengrhee pmainducesvaccineadjuvantactivitybythemodulationoftlrsignalingpathway AT wonkeunoh pmainducesvaccineadjuvantactivitybythemodulationoftlrsignalingpathway AT youngrankim pmainducesvaccineadjuvantactivitybythemodulationoftlrsignalingpathway |