Immunity & infection

Oral Abstract Sessions

Distinct role of Estrogen Receptor α agonist and antagonist on Urinary tract infection outcome in Bladder versus Kidney

Thursday, June 15
4:05 PM - 4:18 PM

Menopause induced hormonal changes in women increase their susceptibility to urinary tract infections (UTIs). FDA approved topical vaginal estrogen prophylaxis is effective in preventing recurrent UTIs but the underlying mechanisms are poorly understood. Using in vitro and in vivo UTI models, we found that estrogen via estrogen receptor α (ERα) alters host immunity in kidney in response to UTI by Dr fimbriae bearing Escherichia coli (E. coli). Time-point infection studies showed delayed interleukin-17 (IL-17) responses in kidneys of ERα gene knockout mice. The present study was conducted to determine the effectiveness of ERα agonist, propyl-pyrazole-triol (PPT), and ERα antagonist, methyl-piperidino-pyrazole (MPP), in bacterial clearance and IL-17 induction in bladder and kidney.

PPT-treated ovariectomized and MPP-treated ovary-intact C3H/HeJ mice were subjected to experimental UTI by E. coli. Bacterial load and IL-17 levels (ELISA and immunohistochemistry) in kidney and bladder were determined at 2 and 6 days post-infection. PPT induced significant decrease in bacterial load and significant induction of IL-17 in kidney (P < 0.05) but on in the bladder. Blocking ERα by MPP compromised bacterial clearance and induction of IL-17 in kidney but showed significant bacterial clearance (P < 0.05) in bladder, however not via IL-17 induction. These studies confirm our previous findings for ERα in kidney where estrogen activates ERα to induce IL-17 production and bacterial clearance while bladder may utilize other estrogen induced receptor mechanisms for protection that need further investigation. These results, showing differential effects of PPT or MPP in bladder and kidney, may have clinical implications for women undergoing hormonal therapy.

Ayantika Sen

Graduate Student
Oklahoma State University Center for Health Sciences

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Janaki Iyer

Post doctoral fellow
Oklahoma State University Center for Health Sciences

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Alexia Dickey

Oklahoma State University-Center for Health Science

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Anil Kaul

Oklahoma State University-Center for Health Sciences

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Chelsea McDonald

Oklahoma State University Center for Health Sciences

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Rashmi Kaul

Oklahoma State University

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Distinct role of Estrogen Receptor α agonist and antagonist on Urinary tract infection outcome in Bladder versus Kidney



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