Escherichia coli-induced inducible nitric oxide synthase and cyclooxygenase expression in the mouse bladder and kidney

Backround. The host response to urinary tract infection includes the produc tion of different inflammatory mediators. We investigated the cellular loca lization and time course of inducible nitric oxide synthase (iNOS) and cycl ooxygenase (COX-2) expression in the mouse bladder and kidney after bacteri al infection. Methods. Experimental urinary tract infection in mice was established by in travesical inoculation of a clinical uropathogen Escherichia coli (E. coli) AD 110. Urine was collected at 6-, 12-, 24-, and 72-hours postinstillation , and the nitrite concentration was determined. The induction of iNOS and C OX-2 was studied by immunohistochemistry and reverse transcription-polymera se chain reaction (RT-PCR). Results. Nitrite levels in the urine had increased threefold at 6 and 12 ho urs postbacterial instillation. Bladders from mice instilled with AD 110, b ut not with phosphate-buffered saline, showed a large number of iNOS- and C OX-2-expressing inflammatory cells. The inflammatory cell activation peaked at 6 and 12 hours postinstillation and had vanished by 72 hours. iNOS expr ession was detected in some urothelial cells after 24 and 72 hours, but COX -2 expression was not detected. In the kidney, infection activated an iNOS and COX-2 response, as shown by immunoreactivity in inflammatory cells at a ll time points. A strong epithelial iNOS response was observed in the renal pelvis at 12, 24, and 72 hours postinstillation, but COX-2 was not detecte d. Enhanced tissue expression of iNOS and COX-2 after bacterial instillatio n was also demonstrated by RT-PCR. Conclusions. E. coli AD 110 induced expression of iNOS and COX-2 in the uri nary tract. Inflammatory cells expressed both iNOS-and COX-2, but epithelia l cells expressed only iNOS and with a later onset than in the inflammatory cells. This suggests that the epithelial iNOS response is not caused by di rect bacterial activation, but more likely is by mediators involved in the inflammatory response.