TNFRp55 signaling controls inflammatory response induced by stimulation with TLR agonists.

JERéZ BELéN; ELIçABE R. JAVIER; JURI AYUB MAXIMILIANO; DI GENARO MARíA SILVIA

Lima

Congreso; Inmunoperu 2012; 2012

Asociacion Latinoamaericana de Inmunologia (ALAI)

TNF plays a key role in inflammation. However, new evidence suggests an anti-inflammatory role for TNF. The mechanisms involved in this effect are unknown. TNFRp55 is the receptor implicated in most TNF effects. In the present work, we studied the impact of TNFRp55 deficiency in macrophages (MÖ) stimulated by a set of agonists to mouse TLR1-9 or Yersinia LPS. We investigated the modulation on nitric oxide (NO) pathway and IL-6 and IL-12/23p40 responses. In addition, we studied the impact of Yersinia LPS stimulacion on IL-12/23p40 mRNA expression and stability. Peritoneal MÖ obtained from C57BL/6 wild-type (WT) and TNFRp55-/- mice were incubated without or with the TLR agonists. Nitrite production in the supernatants was measured using the Griess reagent and the cytokines by ELISA kits. We found higher levels of NO and IL-6 in TNFRp55-/- than WT MÖ stimulated to LPS from E. coli K12 (p<0.05). Yersinia LPS induced higher IL-12/23p40 protein and mRNA in TNFRp55-/- compared to WT MÖ (p<0.05). We observed that the IL-12/23p40 mRNA in LPS-stimulated TNFRp55-/- MÖ has a long half-life (4 hs) after cessation of RNA synthesis by actinomycin D. We concluded that TNFRp55 signaling plays an essential regulatory role modulating NO, IL-6 and IL-12/23p40 production in response to TLR4 stimulation. Transcriptional and post-transcriptional mechanisms may be involved in these effects.