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

الملخص EN

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.