Uropathogenic escherichia coli-induced fibrosis, leading to lower urinary tract symptoms, is associated with type 2 cytokine signaling

Ashlee Bell-Cohn, Daniel J. Mazur, Christel Hall, Anthony J. Schaeffer, Praveen Thumbikat*

*Corresponding author for this work

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Chronic inflammation and prostate fibrosis have been identified as contributors to lower urinary tract symptoms (LUTS) pathophysiology in humans. It has been shown that transurethral infection of an Escherichia coli strain named CP1, which was isolated from a patient with chronic prostatitis, can lead to the develop of differential chronic inflammation and pain in certain mouse strains. Therefore, we hypothesized that differential inflammation would influence fibrotic response in the prostate. This study showed that while prostatic infection by CP1 causes the development of chronic tactile allodynia in NOD/ShiltJ (NOD) but not C57BL/6 (B6) mice, both mice developed evidence of prostate inflammation, prostate fibrosis, and urinary dysfunction. Fibrosis was confirmed by the upregulation of fibrosis-associated messenger RNAs (mRNAs), α-smooth muscle actin immunohistochemistry, and collagen staining with picrosirius red. These findings were mainly focused on the dorsolateral lobes of the prostate. Both mouse strains also developed smaller, more frequent voiding patterns postinfection, examined via cystometry. B6 mice responded to CP1 infection with type 2 cytokines (IL-4 and IL-13), while NOD mice did not, which may explain the differing tactile allodynia responses and level of collagen deposition. When mice lacking signal transducer and activator of transcription 6 (STAT6), a transcription factor known to be important for the production and signaling of IL-4 and IL-13, were infected with CP1, fibrosis was attenuated. This study provides a potential model for studying the development of infection-induced prostatic fibrosis and LUTS. This study also demonstrates that CP1-induced prostate fibrosis has a STAT6-dependent mechanism in B6 mice.

Original languageEnglish (US)
Pages (from-to)F682-F692
JournalAmerican Journal of Physiology - Renal Physiology
Volume316
Issue number4
DOIs
StatePublished - Apr 2019

Keywords

  • Fibrosis
  • LUTS
  • Type 2 cytokine
  • UPEC
  • Urinary dysfunction

ASJC Scopus subject areas

  • Physiology
  • Urology

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