ИСТИНА

Acute pyelonephritis is one of the most frequent infectious diseases of urinary tract and a leading cause of kidney failure worldwide. It is more likely that a key role in kidney damage under pyelonephritis belongs to inflammatory process, rather than bacterial colonization. Preventing or limiting the inflammation and oxidative renal damage during the acute phase should be considered as a major goal in the treatment of pyelonephritis. One strategy for modulating excessive inflammatory responses under pyelonephritis is administration of the mesenchymal multipotent stromal cells (MMSCs). In the present study the putative protective effect of MMSCs against experimental acute pyelonephritis was examined.We found obvious signs of oxidative stress and inflammation in the kidney under acute pyelonephritis in rats. Particularly, pro-inflammatory cytokine TNFα levels, malonyldialdehyde, nitrite and myeloperoxidase activity were considerably increased. Histological evaluation revealed a number of attributes of inflammation and tissue damage in kidney. MMSCs treatment caused a remarkable decrease of all of these pathological signs in renal tissue. Also we showed that activated leukocytes induced preconditioning-like signaling in MMSCs. We showed alterations of expression or activity of iNOS, TGFb, MMP-2 and GSK-3b, which could mediate immunomodulation and protective effects of MMSCs, and these signaling could be characterized as the inflammatory preconditioning. The beneficial capacity of MMSCs to alleviate renal inflammation was more pronounced when preconditioned MMSCs were used.We summarize that MMSCs provide immunomodulatory effects under experimental pyelonephritis by paracrine regulation that depends on the inflammatory microenvironment. This approach could be used to prime MMSCs with different inflammatory modulators to enhance their engraftment and function in an immunoprotective fashion.