RESUMEN
The lipopolysaccharide (LPS) of Gram-negative bacteria is recognized on human monocytes and macrophages by TLR4 and MD2 and induces the production of inflammatory cytokines; the LPSâ¯+â¯IgG complexes co-stimulation increases the cytokine production, mediated by the Fc-γRIIa (CD32a). We stimulated human CD14â¯+â¯monocytes or THP-1 cells with LPS or LPSâ¯+â¯soluble human IgG (sIgG) and TNF-α transcription and production, assessed RT-qPCR, ELISA, or flow cytometry, was enhanced by 30% upon LPSâ¯+â¯sIgG compared to LPS stimulation. LPSâ¯+â¯sIgG co-stimulation affected the NF-κB pathway (p65 phosphorylation and nucleus translocation, and IkB- α degradation). The biochemical inhibition of IRAK 1/4 and Syk kinases suppressed the enhancer effect of LPSâ¯+â¯sIgG on TNF- α production, suggesting the involvement of both MyD88 dependent and independent pathways. Our results suggest that during LPS activation, sIgG may participate in a TLR4 - Fc-γR crosstalk.