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 LPS + IgG complexes co-stimulation increases the cytokine production, mediated by the Fc-γRIIa (CD32a). We stimulated human CD14 + monocytes or THP-1 cells with LPS or LPS + soluble human IgG (sIgG) and TNF-α transcription and production, assessed RT-qPCR, ELISA, or flow cytometry, was enhanced by 30% upon LPS + sIgG compared to LPS stimulation. LPS + 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 LPS + 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.
Keywords: Crosstalk; Fc gamma receptors; Human; Lipopolysaccharide; Monocyte - macrophage; Toll-like receptors.
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