Molecular indicators reflecting the state of stress-limiting systems of whole blood mononuclear leukocytes (MNCs) in patients undergoing community-acquired pneumonia (CAP) were studied.
Purpose of the study. Study of the character of the dependence between the level of phosphorylation of terminal p38 proteinkinase, reflecting the state of the signaling pathway and the content in the cell of components that regulate the processes of proliferation, differentiation and cell death in CAP convalescents. Material and methods. We examined 30 male patients with mild course of bacterial CAP on the 15-17th day of the disease, before their discharging from the hospital. The control group consisted of 15 healthy young people taken from blood donors. Cellular content of MAPK / SAPK and JAK / STAT components of signaling pathways, the content of p53 protein and cytochrome C were evaluated. Also in cell supernatants, the level of molecules controlling apoptosis and proliferation, the members of tumor necrosis factor family (soluble forms of DR5 and DcR3 receptors, ligands TRAL, TWEAK, BAFF, LIGHT), as well as the concentration of antioxidants were investigated. The level of these indicators was investigated depending on the activity of p38 protein kinase, assessed by the level of its phosphorylation. Results. In patients undergoing CAP, on the phone of an increase of the proteinkinase p38 level, takes place an increase of the content of p53 protein in MNC, as well as an increase in the phosphorylation of the inhibitor of the transcription factor of the NF-κB. A statistically significant increase in phosphorylation of protein RB, the soluble form of DR5, TRAIL and BAFF was also detected. These changes were accompanied by a decrease in the level of phosphorylation of JAK2, STAT3 and CREB, as well as the concentrations of TWEAK, LIGHT and cytochrome C. No significant changes in the content of DcR3, STAT5A and AOC were found in groups with different p38 activities. A linear regression analysis revealed a statistically significant positive correlation of p38 activity with the level of phosphorylation of the retinoblastoma protein, STAT3, IκB, JNK and negative with the level of JAK2 phosphorylation. Conclusion. The activity of the MAPK/SAPK signaling pathway in the OLS of SAP convalescents is antagonistic to the JAK/STAT signaling pathway, weakening its activity with a decrease in the sensitivity of cells to the corresponding cytokines. At the same time, an increase of p38 phosphorylation is associated with an increase in IκB phosphorylation, determining the transcription of genes controlling apoptosis, proliferation and cell differentiation. Increased expression of the BAFF gene and increased production of cytokines promotes the activation of B-lymphocytes, while the secretion of TRAIL enhances apoptosis of sensitive cells. Thus, p38 activation in MNCs may contribute to an increase of body resistance and antitumor protection. Thus, the proapoptotic function of p38 could be realized by stimulating p53 production, expression on DR5 cells and their TRAIL production, while the proliferation and differentiation of B lymphocytes can be enhanced by stimulating BAFF production, which is obviously determined by its effect on nuclear transcription through modulation of the functional IκB activity .

Keywords: community-acquired pneumonia, mononuclear leukocytes, p38, DR5, TRAIL, BAFF, IκB