Document Detail


Autocrine effects of interleukin-6 mediate acute-phase proinflammatory and tissue-reparative transcriptional responses of canine bladder mucosa.
MedLine Citation:
PMID:  21115724     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
During early urinary tract infection (UTI) the interplay between invading bacteria and the urothelium elicits a mucosal response aimed at clearing infection. Unfortunately, the resultant inflammation and associated local tissue injury are responsible for patient symptoms. Interleukin-6 (IL-6), a cytokine released during acute UTI, has both pro- and anti-inflammatory effects on other body systems. Within the urothelium, the IL-6 native-tissue origin, the target cell type(s), and ultimate effect of the cytokine on target cells are largely unknown. In the present study we modeled the UTI IL-6 response ex vivo using canine bladder mucosa mounted in Ussing chambers to determine the inflammatory and reparative role of IL-6. We demonstrated that uropathogenic Escherichia coli infection stimulates the synthesis of IL-6 by all urothelial cell layers, with the urothelial cells alone representing the only site of unequivocal IL-6 receptor expression. Autocrine effects of IL-6 were supported by the activation of urothelial STAT3 signaling and SOCS3 expression. Using exogenous IL-6, a microarray approach, and quantitative reverse transcriptase PCR (q-RT-PCR), 5 target genes (tumor necrosis factor alpha, interleukin-1β, matrix metallopeptidase 2, heparan sulfate d-glucosaminyl 3-O-sulfotransferase 3A1, and hyaluronan synthase 2) that have direct or indirect roles in promoting a proinflammatory state were identified. Two of these genes, heparan sulfate d-glucosaminyl 3-O-sulfotransferase 3A1 and hyaluronan synthase 2, are also potentially important mediators of wound repair via the production of glycosaminoglycan components. These findings suggest that IL-6 secretion during acute UTI may serve a dual biological role by initiating the inflammatory response while also repairing urothelial defenses.
Authors:
Michael W Wood; Edward B Breitschwerdt; Jody L Gookin
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-11-29
Journal Detail:
Title:  Infection and immunity     Volume:  79     ISSN:  1098-5522     ISO Abbreviation:  Infect. Immun.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-24     Completed Date:  2011-03-15     Revised Date:  2011-08-03    
Medline Journal Info:
Nlm Unique ID:  0246127     Medline TA:  Infect Immun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  708-15     Citation Subset:  IM    
Affiliation:
Center for Comparative Medicine and Translational Research and Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606, USA.
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MeSH Terms
Descriptor/Qualifier:
Acute-Phase Reaction / metabolism*
Animals
Dogs
Humans
Interleukin-6 / metabolism*
Mucous Membrane / metabolism,  microbiology
Signal Transduction
Tissue Culture Techniques
Urinary Bladder / metabolism*,  microbiology
Uropathogenic Escherichia coli
Urothelium / metabolism
Grant Support
ID/Acronym/Agency:
T32 RR024394/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Interleukin-6
Comments/Corrections

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