Inflammatory response to Escherichia coli urinary tract infection in the neurogenic bladder of the spinal cord injured host

Rajeev Chaudhry, Ramiro J. Madden-Fuentes, Tara K. Ortiz, Zarine Balsara, Yuping Tang, Unwanaobong Nseyo, John S. Wiener, Sherry S. Ross, Patrick C. Seed*

*Corresponding author for this work

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Purpose Urinary tract infections cause significant morbidity in patients with spinal cord injury. An in vivo spinal cord injured rat model of experimental Escherichia coli urinary tract infection mimics human disease with enhanced susceptibility to urinary tract infection compared to controls. We hypothesized that a dysregulated inflammatory response contributes to enhanced susceptibility to urinary tract infection. Materials and Methods Spinal cord injured and sham injured rats were inoculated transurethrally with E. coli. Transcript levels of 84 inflammatory pathway genes were measured in bladder tissue of each group before infection, 24 hours after infection and after 5 days of antibiotic therapy. Results Before infection quantitative polymerase chain reaction array revealed greater than twofold up-regulation in the proinflammatory factor transcripts slc11a1, ccl4 and il1β, and down-regulation of the antimicrobial peptides lcn2 and mpo in spinal cord injured vs control bladders. At 24 hours after infection spinal cord injured bladders showed an attenuated innate immune response with decreased expression of il6, slc11a1, il1β and lcn2, and decreased il10 and slpi expression compared to controls. Despite clearance of bacteriuria with antibiotics spinal cord injured rats had delayed induction of il6 transcription and a delayed anti-inflammatory response with decreased il10 and slpi transcript levels relative to controls. Conclusions Spinal cord injured bladders fail to mount a characteristic inflammatory response to E. coli infection and cannot suppress inflammation after infection is eliminated. This may lead to increased susceptibility to urinary tract infection and persistent chronic inflammation through neural mediated pathways, which to our knowledge remain to be defined.

Original languageEnglish (US)
Pages (from-to)1454-1461
Number of pages8
JournalJournal of Urology
Volume191
Issue number5
DOIs
StatePublished - Jan 1 2014

Fingerprint

Neurogenic Urinary Bladder
Urinary Tract Infections
Spinal Cord
Escherichia coli
Urinary Bladder
Infection
Interleukin-10
Anti-Bacterial Agents
Inflammation
Escherichia coli Infections
Neural Pathways
Bacteriuria
Spinal Cord Injuries
Innate Immunity
Anti-Inflammatory Agents
Theoretical Models
Up-Regulation
Down-Regulation
Morbidity
Polymerase Chain Reaction

Keywords

  • Escherichia coli
  • cytokines
  • neurogenic
  • spinal cord injuries
  • urinary bladder
  • urinary tract infections

ASJC Scopus subject areas

  • Urology

Cite this

Chaudhry, Rajeev ; Madden-Fuentes, Ramiro J. ; Ortiz, Tara K. ; Balsara, Zarine ; Tang, Yuping ; Nseyo, Unwanaobong ; Wiener, John S. ; Ross, Sherry S. ; Seed, Patrick C. / Inflammatory response to Escherichia coli urinary tract infection in the neurogenic bladder of the spinal cord injured host. In: Journal of Urology. 2014 ; Vol. 191, No. 5. pp. 1454-1461.
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Chaudhry, R, Madden-Fuentes, RJ, Ortiz, TK, Balsara, Z, Tang, Y, Nseyo, U, Wiener, JS, Ross, SS & Seed, PC 2014, 'Inflammatory response to Escherichia coli urinary tract infection in the neurogenic bladder of the spinal cord injured host', Journal of Urology, vol. 191, no. 5, pp. 1454-1461. https://doi.org/10.1016/j.juro.2013.12.013

Inflammatory response to Escherichia coli urinary tract infection in the neurogenic bladder of the spinal cord injured host. / Chaudhry, Rajeev; Madden-Fuentes, Ramiro J.; Ortiz, Tara K.; Balsara, Zarine; Tang, Yuping; Nseyo, Unwanaobong; Wiener, John S.; Ross, Sherry S.; Seed, Patrick C.

In: Journal of Urology, Vol. 191, No. 5, 01.01.2014, p. 1454-1461.

Research output: Contribution to journalArticle

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T1 - Inflammatory response to Escherichia coli urinary tract infection in the neurogenic bladder of the spinal cord injured host

AU - Chaudhry, Rajeev

AU - Madden-Fuentes, Ramiro J.

AU - Ortiz, Tara K.

AU - Balsara, Zarine

AU - Tang, Yuping

AU - Nseyo, Unwanaobong

AU - Wiener, John S.

AU - Ross, Sherry S.

AU - Seed, Patrick C.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Purpose Urinary tract infections cause significant morbidity in patients with spinal cord injury. An in vivo spinal cord injured rat model of experimental Escherichia coli urinary tract infection mimics human disease with enhanced susceptibility to urinary tract infection compared to controls. We hypothesized that a dysregulated inflammatory response contributes to enhanced susceptibility to urinary tract infection. Materials and Methods Spinal cord injured and sham injured rats were inoculated transurethrally with E. coli. Transcript levels of 84 inflammatory pathway genes were measured in bladder tissue of each group before infection, 24 hours after infection and after 5 days of antibiotic therapy. Results Before infection quantitative polymerase chain reaction array revealed greater than twofold up-regulation in the proinflammatory factor transcripts slc11a1, ccl4 and il1β, and down-regulation of the antimicrobial peptides lcn2 and mpo in spinal cord injured vs control bladders. At 24 hours after infection spinal cord injured bladders showed an attenuated innate immune response with decreased expression of il6, slc11a1, il1β and lcn2, and decreased il10 and slpi expression compared to controls. Despite clearance of bacteriuria with antibiotics spinal cord injured rats had delayed induction of il6 transcription and a delayed anti-inflammatory response with decreased il10 and slpi transcript levels relative to controls. Conclusions Spinal cord injured bladders fail to mount a characteristic inflammatory response to E. coli infection and cannot suppress inflammation after infection is eliminated. This may lead to increased susceptibility to urinary tract infection and persistent chronic inflammation through neural mediated pathways, which to our knowledge remain to be defined.

AB - Purpose Urinary tract infections cause significant morbidity in patients with spinal cord injury. An in vivo spinal cord injured rat model of experimental Escherichia coli urinary tract infection mimics human disease with enhanced susceptibility to urinary tract infection compared to controls. We hypothesized that a dysregulated inflammatory response contributes to enhanced susceptibility to urinary tract infection. Materials and Methods Spinal cord injured and sham injured rats were inoculated transurethrally with E. coli. Transcript levels of 84 inflammatory pathway genes were measured in bladder tissue of each group before infection, 24 hours after infection and after 5 days of antibiotic therapy. Results Before infection quantitative polymerase chain reaction array revealed greater than twofold up-regulation in the proinflammatory factor transcripts slc11a1, ccl4 and il1β, and down-regulation of the antimicrobial peptides lcn2 and mpo in spinal cord injured vs control bladders. At 24 hours after infection spinal cord injured bladders showed an attenuated innate immune response with decreased expression of il6, slc11a1, il1β and lcn2, and decreased il10 and slpi expression compared to controls. Despite clearance of bacteriuria with antibiotics spinal cord injured rats had delayed induction of il6 transcription and a delayed anti-inflammatory response with decreased il10 and slpi transcript levels relative to controls. Conclusions Spinal cord injured bladders fail to mount a characteristic inflammatory response to E. coli infection and cannot suppress inflammation after infection is eliminated. This may lead to increased susceptibility to urinary tract infection and persistent chronic inflammation through neural mediated pathways, which to our knowledge remain to be defined.

KW - Escherichia coli

KW - cytokines

KW - neurogenic

KW - spinal cord injuries

KW - urinary bladder

KW - urinary tract infections

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