Understanding the response of dendritic cells to activation by streptococcal preparation OK-432.
BACKGROUND
The streptococcal preparation OK-432 induces maturation of T cells and dendritic cells (DCs). However, the mechanisms by which OK-432 induces DC maturation are not well understood.


METHODS
The effects of OK-432 and TNF-alpha on peripheral blood mononuclear cells (PBMCs) were compared. Antibody-based approaches were used to detect proteins characteristic of antigen-presenting cells and cytokines. Cytotoxicity was evaluated by measuring the release of LDH after incubation of effector and target cells. The TLR-4 levels were measured by real-time quantitative PCR.


RESULTS
Changes in cell surface marker levels were detected in both treatment groups but OK-432 had a greater effect on induction of Th-1-type cytokines. Furthermore, TLR-4 mRNA was up-regulated in cells from two out of five patients in response to OK-432, but not in response to TNF-alpha.


CONCLUSIONS
OK-432 has a more profound effect on human DCs than TNF-alpha and may act through multiple signaling pathways.
Kanzaki
Norio
N
Department of Surgery 1, Fukushima Medical University, Fukushima 960-1295, Japan.
Terashima
Masanori
M
Kashimura
Seigo
S
Hoshino
Mika
M
Ohtani
Satoshi
S
Matsuyama
Shinichi
S
Hoshino
Yutaka
Y
Kogure
Michihiko
M
Oshibe
Ikurou
I
Endo
Hisahito
H
Saito
Takahiro
T
Yaginuma
Hiroshi
H
Gotoh
Mitsukazu
M
Ohto
Hitoshi
H
D000328:Adult; D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D010844:Picibanil / Q000276:immunology / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology; D015854:Up-Regulation
D016207:Cytokines; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D010844:Picibanil