탄저 캡슐항원에 의한 사람 면역세포 반응 및 면역 기전 연구

초록

Purpose : The capsule of Bacillus anthracis, poly-Y-D-glutamic acid(PGA)， functions as a virulence determinant. Recent reports suggested the possibility of PGA capsule as a target for vaccine development. However, innate immune response of PGA has not been investigated. In this study， we have characterized the innate immune response elicited by the PGA capsule component in the human monocytic cell lines， THP-1， differentiated into macrophage with phorbol 12-myristate 13-acetate(PMA). Methods : PGA was purified either from the bacterial culture supernatant of Bacillus licheniformis or from the culture supernatant of pXOl cured B. anthracis(H9401). The purifed PGA from B. licheniformis was degraded to 30 kDa size by acid hydrolysis. Results : PGA treatments induced specific extracellular releases of interleukin IL-lβ and TNF-α of differentiated THP-1 cells in dose-dependent manner. The addition of polymyxin B did not affect the inductions, which indicates that the induction was not due to the contamination of endotoxin which might be existed in the PGA fraction. The increases of cytokine productions were inhibited by TLR2-blocking antibody， TL2.1. and by selective inhibitors of ERK1/2，JNK/SAPK and p38 kinases. In addition， the administration of an IL-1-converting enzyme/Caspase-1(ICE)-specific inhibitor prior to PGA treatment blocked induction of cytokines in dose-dependent manner. Conclusions : Our results suggest that PGA-induced IL-lβ and TNF-α secretion occurred via activation of ERK1/2，JNK/SAPK and p38 through TLR2 pathways in PMA-differentiated THP-1 cells. In addition，capase-1 was involved in PGA-induced IL-lβ and TNF-α secretion.

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