Extracellular Cold Shock Protein YB-1 Induces Tolerance to GMDP and LPS in Mouse Macrophage Cell Line J774

— A cold shock protein YB-1 is involved in the regulation of many fundamental biological processes. Previously, we demonstrated that YB-1 is also involved in the process of recognition of GMDP muramyl peptide by the NOD2 innate immunity system receptor and is able (upon preliminary administration) to protect mice from death in a model of septic shock induced by Escherichia coli bacteria. We hypothesized that the protective effect of YB-1 can be associated with the development of a state of tolerance (“nonresponse”). We tested the possibility of tolerance induction by the YB-1 protein in a model system on a J774 mouse macrophage cell line with the involvement of cell wall components of E. coli bacteria (GMDP (NOD2 receptor agonist) and LPS (TLR4 receptor agonist) immunostimulants). Changes in the cell response were estimated by the level of mRNA expression of the target molecules by a method of quantitative PCR analysis combined with reverse transcription. Upon pretreatment of cells with YB-1, there was a significant decrease in the level of mRNA expression of proinflammatory cytokines (IL-1β, TNF-α, and IL-6) in response to further stimulation with GMDP and LPS, as well as significant changes that were detected in the expression of mRNA of RIP2 and MyD88 adapter molecules and components of NF-κB transcription factor. Our data demonstrate that YB-1 is able to induce a tolerance to immunostimulants (such as GMDP and LPS) apparently due to an increase in the production of IL-1Ra anti-inflammatory cytokine and SOCS1 inhibitor. A more precise characterization of the peculiarities of YB-1-induced state of tolerance requires further studies.