INFLUENCE OF INFLUENZA A VIRUS AND BACTERIAL LIPOPOLYSACCHARIDE ON PROLIFERATION AND GENE EXPRESSION OF CYTOKINES AND OTHER CELLULAR FACTORS IN CELLS OF ESTABLISHED ENDOTHELIAL CELL LINE ECV-304.

Change of state of endothelial cells occurs under the action of viral infection and bacterial lipopolysaccharide (LPS) that leads to cell dysfunction. Therefore, the aim of the current study was to investigate the effect of LPS from Escherichia coli and influenza A virus on proliferative activity of human endothelial cells (ECV-304) and gene expression of several cytokines and cellular factors: TNFá, TGFâ, IFN-ã, MMP-9, NF-êB, Rho A, eNOS and iNOS. It was found that ECV-304 cells once infected with very low infectious doses of influenza virus acquire the ability to long-term active proliferation (over 8 passages). Addition of LPS E. coli reduced the virus-stimulated cell proliferation. It was shown that influenza virus and LPS can affect on gene expression of cytokine and other cellular factors. When endothelial cells had been infected with influenza A virus in the presence of LPS, there was a significant increase in the expression of several genes and replacement of some genes expression on the expression of other genes. Expression of MMP-9 gene was inhibited in the case of separate exposure to the virus and LPS, but it was significantly increased during the first day under the adding of the virus and LPS together, as well as the activity of the IFN-ã gene; gene of TNFá was active for only 1—3 days whereas genes expression of other factors (TGFâ, eNOS, iNOS, NF-êB and Rho A) increased significantly at the 5th day as in the case of adding only LPS. Thus, the change of physiological state of endothelial cells occurs in the presence of influenza A virus and LPS and it can be caused during different time periods (as well as by varying degrees of virus infection of cells) by different cellular factors and possibly with involvement of different signaling pathways.