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.

ABSTRACT

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.