TcpC secreting uropathogenic E. coli promoted kidney cells to secrete MIP-2 via p38 MAPK pathway

He,Yujie; Fang,Jie; Zhang,Chong; Pan,Jun; Jin,Qi; Yang,Yingzhi; Wang,Linyao; Wang,Baoming; Zhang,Dayong; Pan,Jianping

doi:10.3892/mmr.2017.7021

TcpC secreting uropathogenic E. coli promoted kidney cells to secrete MIP-2 via p38 MAPK pathway

Authors:
- Yujie He
- Jie Fang
- Chong Zhang
- Jun Pan
- Qi Jin
- Yingzhi Yang
- Linyao Wang
- Baoming Wang
- Dayong Zhang
- Jianping Pan
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Affiliations: Department of Clinical Medicine, School of Medicine, Zhejiang University City College, Hangzhou, Zhejiang 310015, P.R. China, Cancer Institute, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310007, P.R. China
Published online on: July 17, 2017 https://doi.org/10.3892/mmr.2017.7021
Pages: 3528-3534

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Abstract

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/interleukin‑1 receptor domain‑containing protein C (TcpC) encoded by E. coli is an important virulence factor in the majority of strains of UPEC and inhibits macrophage‑mediated 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 protein‑2 (MIP‑2; also known as C‑X‑C motif chemokine 2). MIP‑2 concentration in kidney homogenates from TcpC‑secreting UPEC CFT073 (TcpCwt) murine pyelonephritis models was significantly higher compared with that in kidney homogenates from tcpC knockout CFT073 (TcpC‑/‑) models. In vitro, TcpCwt dose‑dependently promoted MIP‑2 secretion in HEK‑293 cells. The concentration of MIP‑2 in culture supernatants of HEK‑293 co‑cultured with TcpCwt was profoundly higher compared with that of HEK‑293 co‑cultured with TcpC‑/‑. In the presence of anti‑TcpC antibody, the enhancement effect of TcpCwt on MIP‑2 production was completely abrogated, suggesting that the enhanced production of MIP‑2 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 HEK‑293 cells, as indicated by a simultaneous increase in p38 and phosphorylated‑p38. In addition, inhibition of p38 MAPK with SB203580 significantly decreased MIP‑2 concentration and neutrophil recruitment activity in the supernatants of HEK‑293 cells co‑cultured with TcpCwt. This indicates that TcpC may promote MIP‑2 production in kidney cells through the p38 MAPK signaling pathway. Taken together, the data of the present study demonstrated that TcpC can induce MIP‑2 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 TcpC‑secreting UPEC.

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