Inhibitory Effect of Transcription Factor YB-1 in the Development of Signal from an Innate Immunity Receptor NOD2

Abstract

It was shown that in the presence of the recombinant protein YB-1, the response of human leukemic monocytes THP-1 to stimulation with muramylpeptide GMDP and LPS was significantly reduced, which was manifested in a decrease of the relative content of mRNA encoding the following molecules: proinflammatory cytokine IL-1β, innate immunity receptors NOD2 and TLR4, their adapters RIP2 and MyD88, and the p105/p50 (NF-κB1) and p100/p52 (NF-κB2) subunits of the NF-κB transcription factor. The inhibiting effect of YB-1 protein also follows from the lower level of p65 protein (RelA NF-kB) in nuclei of cells stimulated with LPS and GMDP/LPS. Inactivation of the NOD2 gene in the THP-1 cells resulted in a decrease of IL-1β mRNA in response to GMDP, LPS, and GMDP/LPS. At the same time, inactivation of the YB-1 gene led to an increased relative content of IL-1β and other molecules’ mRNA upon stimulation with GMDP. However, in response to stimulation with LPS and GMDP/LPS the level of IL-1β mRNA decreased in comparison to the initial cells, which indicates that YB-1 is necessary for the induction of an optimal immune response. Thus, the data obtained indicate the involvement of YB-1 in the innate immunity receptor system as a negative regulator of NOD2 receptor activity.