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SYNERGISTIC ACTIVATION OF INOS, IFN-Β, IL12P40, IL6, TNF-Α GENES TRANSCRIPTION IN MACROPHAGES UNDER SIMULTANEOUS INFLUENCE WITH AGONISTS OF TLR4, TLR9 AND NOD2 RECEPTORS


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Abstract

Combined stimulation of two or more pattern recognition receptors (PRRs) can synergistically activate cells of immune system and ultimately confer effective immune defense against infections. Here, we evaluated the activation impact of the triple composition of TLR4, TLR9 and NOD2 receptors’ agonists on mouse bone marrow-derived macrophages according to mRNA-expression of tnf-α, il6, il12p40 cytokines as well as ifn-β and inos genes. Macrophage response to the triple agonistic composition was compared to the one induced with the same PRR-agonists used as a paired or single compounds. It was shown that macrophage stimulation with the paired or triple combinations of NOD2, TLR4 and TLR9 agonists induced much stronger, synergistic, expression of tnf-α, il6, il12p40, ifn-β and inos mRNA as compared to the transcription induced by the same agonists used alone. Triple was stronger than paired combination of PRR-agonists in induction of il12p40 and inos, but not of tnf-α genes transcriptional response in macrophages. Our data suggest that concordant stimulation of TLR4, TLR9 and NOD2 receptors synergistically induces macrophage response on the level of proinflammatory cytokines and antimicrobial compounds genes’ transcription.


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