Enhanced chemokine response in experimental acute Escherichia coli pyelonephritis in IL‐1β‐deficient mice

• Published in: Clinical and experimental immunology 2003-02, Vol.131 (2), p.225-233
• Main Authors: HERTTING, O., KHALIL, A., JAREMKO, G., CHROMEK, M., LI, Y.‐H., BAKHIET, M., BARTFAI, T., TULLUS, K., BRAUNER, A.
• Format: Article
• Language: English
• Subjects: Bacterial diseases; Bacterial diseases of the urinary system; Biological and medical sciences; Human bacterial diseases; Infectious diseases; MCP‐1 MIP‐2/IL‐8 RANTES acute pyelonephritis E. coli; Medical sciences; Original
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1046/j.1365-2249.2003.02076.x

SUMMARY The aim of the present study was to investigate the effects of IL‐1β and Escherichia coli on the expression and secretion of MIP‐2, the mouse equivalent to human IL‐8, MCP‐1 and RANTES in the kidneys of mice with acute pyelonephritis. Female Bki NMRI, as well as IL‐1β deficient mice and their wild‐type littermates, were transurethrally infected with either E. coli CFT 073 or injected with NaCl 0·9% (w/v) and thereafter obstructed for 6 h. The Bki NMRI mice were killed at 0, 24, 48 h and 6 days and the IL‐1β‐deficient mice at 48 h. Chemokine mRNA and protein levels peaked at 24 h for the tested chemokines with the mRNA expression localized in the tubular epithelial cells and for MIP‐2 also in neutrophils. Obstruction per se, also induced a chemokine expression similar to E. coli infection although at a lower level. Interestingly, MIP‐2 levels were higher in the IL‐1β deficient mice as compared with the wild‐type littermates. Likewise, the inflammatory changes were more frequent and, when present, more widespread in the IL‐1β‐deficient mice than in the wild‐type mice. Stimulation of a human renal tubular epithelial cell line (HREC), A498 and of primary human mesangial cells (HMC) with the same bacterial antigen depicted gene expression of the same chemokines. A rapid release of IL‐8 and MCP‐1 was observed from both cell types. RANTES response was delayed both in the HREC and the HMC. We conclude that acute E. coli pyelonephritis induces a MIP‐2/IL‐8, MCP‐1 and RANTES expression and secretion localized primarily to the epithelial cells and that this production is confirmed after in vitro stimulation with the same bacterial antigen of human epithelial and mesangial cells. Blockade of induction of chemokine response may thus be an attractive target for possible therapeutic intervention.