Influence of muramyl peptides on the production of chemokines, growth factors, pro-inflammatory and anti-inflammatory cytokines

Abstract

Relevance.The recent increase in inflammatory, allergic and infectious diseases needs to update new ways of raising non-specific resistance of the organism. Innate immunity provides the first line of defense against pathogens through the activation of receptors that detect microorganisms: TLRs, NLRs and CLRs. Muramyl peptides that form the cell wall of all known bacteria are recognized by NLRs and trigger immune responses to eliminate pathogens. The aim of this study was to investigate the effect of muramyl peptides on the production of chemokines, growth factors, pro-inflammatory and anti-inflammatory cytokines by human mononuclear cells.Materials and Methods.Mononuclear cells were isolated from the peripheral blood of healthy volunteers using the Cell Separation Media Lympholyte CL 5015 reagent and cultured for 4 hours in the presence of glucosaminyl muramyl dipeptides GMDP, GMDP-OH, GMDP-Lys, GMDP-LL; an adequate amount of medium was added to the control wells. The levels of chemokines, growth factors, proinflammatory and anti-inflammatory cytokines were measured using magnetic beads with antibodies according to the manufacturer’s instructions Luminex 200, Merck (Millipore) equipment, and software (Burlington, Massachusetts, USA).Results and Discussion.It was found that muramyl peptides GMDP, GMDP-ON and GMDP-Lys enhance the production of cytokines IL-1a, IL-1b, IL-1RA, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12P40, IL-12P70, IL-15, MDC, sCD40L, IFNα2, IFN-γ, TNF-a, TNF-β, GM-CSF. GMDP-LL does not affect the production of cytokines. At the same time, muramyl peptides with the L-configuration of alanine and the D-configuration of isoglutamine (L-D muramyl peptides) did not change the values of IL-2, IL-3, IL-5, IL-9.Conclusion.The D-configuration of isoglutamine is fundamental for the implementation of the regulatory activity of muramyl peptides. Awide range of bacterial bioregulators, the source of which are microorganisms, regulate the host homeostasis and trigger immune reactions, which, depending on the context, can have opposite effects. L-D muramyl peptides activate mononuclear cells, which begin to produce proinflammatory cytokines and chemokines, as well as growth factors necessary for the destruction of pathogens. In addition, anti-inflammatory cytokines are also triggered, which have aregulatory role in the appearance of memory cells and the weakening of inflammatory reactions. Thus, normally, muramyl peptides participate in maintaining tolerance to microflora and maintaining immune homeostasis.

Keywords

• innate immunity
• immune homeostasis
• tolerance
• glucosaminylmuramyldipeptide
• muramyl peptide
• inflammation regulation
• bacterial bioregulators
• nod2
• nod2