REGULATORY EFFECT OF TNF ON IL-12/23P40 PRODUCTION BY MURINE DENDRITIC CELLS

MAYORDOMO ANDREA CONSTANZA; ARIAS JOSÉ LUIS; SILVA JUAN EDUARDO; GORLINO CAROLINA VIRGINIA; DI GENARO MARIA SILVIA

Villa de Merlo, San Luis

Congreso; XXXV Reunion Cientifica Anual de la Sociedad de Biología de Cuyo; 2017

Sociedad de Biologia de Cuyo

TNF is a pleiotropic cytokine considered a major player in the initiation and orchestration of complex events in inflammation and immunity. The biological activities of TNF are mediated by two receptors, TNFRp55 and TNFRp75. TNFRp55 is the primary signaling receptor for the majority of the pro-inflammatory and cytotoxic effects classically attributed to TNF. The purpose of the present work was to know how TNFRp55 signaling modulates IL-12/23p40 production. Isolated splenic wild-type (WT) or TNFRp55-/- DC were stimulated with LPS in presence and absence of TNF or TNF inhibitors. The levels of IL-12/23p40 and IL-10 were assessed in culture supernatants by ELISA. We found that TNF significantly decreased the IL-12/23p40 secretion by LPS-stimulated WT DC. This regulatory effect was not observed in TNFRp55-/- DC. Moreover, the TNF antagonist, Etanercept, decreased IL-12/23p40 secretion in LPS-stimulated WT and TNFRp55-/- DC, suggesting a TNFRp75-depending IL-12/23p40 production by DC. When TNF-TNFRp55 pathway was analyzed using the specific inhibitor CAY10500, we observed that the regulatory effect of TNF on IL-12/23p40 secretion in WT DC was lost. This result mirrored the effect of TNF on LPS-stimulated TNFRp55-/- DC. Interesting, IL-10 amounts were not modified by Etanercept in WT as well as in TNFRp55-/- DC. However, IL-10 levels resulted significantly reduced by CAY10500 in LPS-stimulated WT DCs, but not in TNFRp55-/- DC. These data indicate that IL-10 seem to mediate the regulatory effect of the TNFRp55 pathway on IL-12/23p40 secretion by LPS-stimulated DC.