Prostate carcinoma cells LNCaP differentially regulate cytokine release in dectin 1- and Toll-like receptor- stimulated human monocyte-derived dendritic cells

We investigated the effects of prostate carcinoma cells LNCaP on human DC maturation, superoxide anion and cytokine production. LNCaP promoted partial DC maturation and scarce IL-12 secretion. The dectin 1 agonist glucan, an immuno-stimulating agent able to induce DC maturation but not IL-12 production, increased IL-12 release by DC cultured with LNCaP. Interestingly, LNCaP decreased superoxide anion production, but enhanced IL-1β, IL-23, IL-6 and TNF-α secretion in glucan-stimulated DC. Conversely LNCaP did not affect IL-1β, IL-23 and TNF-α, but inhibited IL-12 and IL-6 secretion induced by Toll-like receptors agonists LPS and Pam3CSK4, that elicit DC maturation but not superoxide anion generation. The NADPH oxidase inhibitor DPI and the superoxide anion scavenger SOD increased dectin 1-dependent IL-1β, IL-23, IL-6 and TNF-α release by DC, reproducing the effect of LNCaP, but did not affect IL-12 secretion by glucan-stimulated DC and cytokine release in LPS- or Pam3CSK4-treated DC both in presence or absence of LNCaP. Conditioned media of DC co-cultured with LNCaP activated IFN-γ production by natural killer cells and modulated IFN-γ and IL-17 release by CD4+ lymphocytes. Experiments performed with an IL-12-blocking antibody demonstrated that these effects arise from LNCaP- and glucan-dependent regulation of IL-12 production by DC. Our results indicate that LNCaP modulate DC cytokine release through NADPH oxidase-related or NADPH oxidase-unrelated mechanisms, depending on the type of cytokine secreted and/or receptor engaged when DC interact with tumor cells. The LNCaP-elicited IL-12 production by DC is enhanced by glucan and deeply influences the activity of natural killer cells and CD4+ lymphocytes.