The pivotal role of p38 and NF-kappaB signal pathways in the maturation of human monocyte-derived dendritic cells stimulated by streptococcal agent OK-432.
OK-432, a streptococcal preparation, has been shown as an effective activator to induce human monocyte-derived dendritic cells maturation. During this process, the activation of Toll-like receptor 4 plays an important role. However, the signaling pathway involved in has not been fully understood. In the present study, we investigated the underlying mechanisms, by which OK-432 induced maturation of human monocyte-derived DCs (MoDCs). We observed that exposure of immature MoDCs to OK-432 activated the p38 MAPK and NF-kappaB pathway, accompanied up-regulated the surface expression of maturation markers CD80, CD83, CD86 and HLA-DR, increased secretion of TNF-alpha, IL-12 and chemokine, IP-10. In addition, T cells stimulatory capacity was also enhanced. The maturation of MoDCs stimulated by OK-432 was inhibited by treatment with p38 pathway inhibitor, SB203580, or NF-kappaB pathway inhibitor, BAY-117082. Whereas, blocking of JNK pathway with SP600125 or ERK pathway with PD98059 did not influence OK-432-induced DCs maturation. Taken together, our data indicated that OK-432-induced DCs maturation was due, at least partly to the activation of p38 and NF-kappaB pathway.
The State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Sun Yat-sen University Cancer Center, District, Guangzhou, Guangdong Province 510060, PR China.
Ke
K
Pan
Hui
H
Wang
Wan-li
WL
Liu
Hua-kun
HK
Zhang
Jun
J
Zhou
Jian-jun
JJ
Li
De-sheng
DS
Weng
Wei
W
Huang
Jian-cong
JC
Sun
Xiao-ting
XT
Liang
Jian-chuan
JC
Xia
D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D018664:Interleukin-12 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010844:Picibanil / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013291:Streptococcus; D013450:Sulfones / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism*
C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D018122:B7-1 Antigen; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D007093:Imidazoles; D016328:NF-kappa B; D009570:Nitriles; D011725:Pyridines; D013450:Sulfones; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D010844:Picibanil; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580