Pro-inflammatory Factors Regulate Expression Of Nerve Growth Factor And Its Receptors On Human Dendritic Cells And The Related Signal Transduction Pathways

Weak expression of NGF and absence of its receptors were observed in immature MoDCs. However, LPS not CpG ODN could up-regulate the p75^NTR expression and NGF secretion dose- and time-dependently in p38 MAPK and or NF-kB dependent manner. When p75^NTR on MoDCs was activated by NGF following LPS stimulation, resulting MoDCs expressed a high surface expression of MHC class II and costimulatory molecules, an enhanced AMLR, an increase of cytokines secretion and CCR7 expression, and a decreased capacity to internalize Ags. NGF induced phosphorylation of Erk, p38MAPK and nuclear translocation of p65 on LPS pre-stimulated MoDCs and blockade of p38MAPK and NF-kB could inhibit secretion of IL-12 and TNF-a from LPS pre-stimulated MoDCs by NGF, suggesting NGF acted on MoDCs through activation of p38 MAPK and NF-kB pathway.