Antagonism of macrophage migration inhibitory factor decreases cyclophosphamide cystitis in mice

Neurourology and Urodynamics
Pedro L VeraKatherine L Meyer-Siegler

Abstract

Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine found pre-formed in the urothelium. During inflammation, MIF is released into the bladder lumen and bladder MIF mRNA is upregulated. Since MIF also has tautomerase activity and blocking tautomerase activity also blocks MIF's biological activity, we hypothesized that blocking MIF's tautomerase activity would prevent bladder inflammation. Therefore, we examined the effects of a MIF tautomerase inhibitor (ISO-1; also blocks biological activity) on cyclophosphamide (CYP)-induced cystitis in mice. Mice receiving CYP (300 mg/kg; i.p.) to induce cystitis or saline (control) were treated either with ISO-1 (20 mg/kg; i.p.; daily) or vehicle (20% DMSO; i.p.; daily) for 2 days. After 2 days, micturition volume and frequency in awake mice were recorded and also mechanical sensitivity to abdominal stimulation using von Frey monofilaments. Bladders were collected under anesthesia and examined histologically, nerve growth factor levels were assayed in bladder homogenates, and production of inflammatory cytokines in the bladder was determined using a targeted array. CYP treatment resulted in decreased micturition volume, increased frequency, decreased threshold, increa...Continue Reading

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Citations

Mar 25, 2011·Future Medicinal Chemistry·Yousef Al-Abed, Sonya VanPatten
Apr 27, 2011·Neurourology and Urodynamics·Peter OchodnickýMartin C Michel
Sep 4, 2012·Magyar sebészet·Péter JáromiPetra Hartmann
May 29, 2015·PloS One·Dimitrios E KouzoukasPedro L Vera
Mar 25, 2016·PloS One·Dimitrios E KouzoukasPedro L Vera
Jan 24, 2018·American Journal of Physiology. Renal Physiology·Wenfu WangYaofeng Zhu
Aug 17, 2018·International Journal of Urology : Official Journal of the Japanese Urological Association·Fei MaPedro L Vera

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