RESUMO
Pyelonephritis is an infection of the upper urinary tract with characteristic histological change to neutrophil infiltration in the kidney. The majority of pyelonephritis is caused by uropathogenic Escherichia (E.) coli (UPEC) bearing distinct virulence factors. Toll/interleukin1 receptor domaincontaining protein C (TcpC) encoded by E. coli is an important virulence factor in the majority of strains of UPEC and inhibits macrophagemediated innate immunity, which serves an essential role in the pathogenesis of pyelonephritis. In the present study, it was demonstrated that TcpC induced kidney cells to produce macrophage inflammatory protein2 (MIP2; also known as CXC motif chemokine 2). MIP2 concentration in kidney homogenates from TcpCsecreting UPEC CFT073 (TcpCwt) murine pyelonephritis models was significantly higher compared with that in kidney homogenates from tcpC knockout CFT073 (TcpC/) models. In vitro, TcpCwt dosedependently promoted MIP2 secretion in HEK293 cells. The concentration of MIP2 in culture supernatants of HEK293 cocultured with TcpCwt was profoundly higher compared with that of HEK293 cocultured with TcpC/. In the presence of antiTcpC antibody, the enhancement effect of TcpCwt on MIP2 production was completely abrogated, suggesting that the enhanced production of MIP2 was mediated by secreted TcpC. Furthermore, it was demonstrated that TcpC/ treatment had no effect on the p38 mitogen activated protein kinase (MAPK) signaling pathway, while TcpCwt treatment resulted in the activation of p38 MAPK in HEK293 cells, as indicated by a simultaneous increase in p38 and phosphorylatedp38. In addition, inhibition of p38 MAPK with SB203580 significantly decreased MIP2 concentration and neutrophil recruitment activity in the supernatants of HEK293 cells cocultured with TcpCwt. This indicates that TcpC may promote MIP2 production in kidney cells through the p38 MAPK signaling pathway. Taken together, the data of the present study demonstrated that TcpC can induce MIP2 production, which may contribute to the characteristic histological change associated with pyelonephritis. This data has provided novel evidence to further clarify the pathogenesis of pyelonephritis and novel directions on the pathogenicity of TcpCsecreting UPEC.