CONDITION OF RIG-IAND NF-KB-SIGNAL PATHWAYS IN MONONUCLEAR CELLS OF WHOLE BLOOD OF PRACTICALLY HEALTHY PEOPLE AND RECONVENCENTS OF PNEUMONIA AFFECTED BY MITOGENIC STIMULATION

Abstract

The key role in the antiviral and antimicrobial defense of the body is played by the RIG-I and NF-kB signaling pathways. The RIG-I signaling pathway activates interferon-regulated factors IRF3 and IRF7, and the central component of the NF-kB signaling pathway, the nuclear transcription factor NF-kB, determines the production of endogenous antimicrobial peptides and interferons by cells. One of the key regulators of the RIG-I signaling pathway is the mitochondrial protein MAVS, which integrates signals from receptors that recognize pathogenicity patterns. The influence of various factors, such as bacterial toxins, free radicals, reactive oxygen species, leads to MAVS dysfunction, impaired antiviral resistance and the progression of viral infection. However, despite the important role of the proteins of the RIG-I-pathway and the components of the NF-KB-signaling pathway in ensuring the body's resistance to infections and sanogenesis, their significance in the postclinical phase has not been fully studied. The aim of the study was to evaluate the content of the components of RIG-I and NF-kB signaling pathways in mononuclear cells of whole blood of healthy individuals and pneumonia convalescents after exposure to a complex mitogen. The enzyme-linked immunosorbent assay determined the content of components of the NF-kB signaling pathway (p50, p65, c-Rel, RelB, NF-kB2), protein kinases of the NF-kB nuclear transcription factor inhibitor (IkB), and RIG-I- proteins in mononuclear cells of whole blood the signal path (TAK1, TBK1, TRIM25, TMEM173, RNF125, IRF3, IRF7, MAVS), RIG-I-dependent helicase (LGP2), the level of phosphorylation of protein kinase p38 and IkB, as well as the production of whole blood cells IL-4, IL-, were evaluated 12, RANTES, cathelicidin and interferons (IFN-p and IFNa). It was established that in the subclinical phase of community-acquired bacterial pneumonia in mononuclear cells of whole blood after stimulation with a complex mitogen containing lipopolysaccharide, the content of RelB, MaVS, DHX58, and IRF7 decreased compared to practically healthy individuals, p38 protein kinase dephosphorylation was noted. In contrast, the concentrations of IKKa, IKKp, the level of phosphorylation of kBa, the protein content of TRIM25, TMEM173, OTuD5, RNF125 and tBk1 were increased. These changes were accompanied by a statistically significant decrease in the production of IL-4, IL-12, RANTES, cathelicidin and IFN-p against the background of an increase in the level of IFNa. The effect on the mononuclear cells of whole blood of a complex mitogen led to a change in the ratio of the components of the signaling pathways that determine the antibacterial and antiviral defense of the body. In patients with pneumonia, against the background of mitogenic stimulation, the production of cathelicidin,