Up-regulation of interleukin-6 gene expression in cyclophosphamide-induced cystitis in mice: An in situ hybridization histochemical study

Int J Urol. 2006 Oct;13(10):1339-43. doi: 10.1111/j.1442-2042.2006.01536.x.

Abstract

Aim: To determine the time course and the cellular sources of interleukin (IL)-6 in the bladder during experimental cystitis, the expression of the IL-6 gene and IL-6 protein was examined in the bladder during cyclophosphamide (CP)-induced cystitis.

Methods: Mice were killed at 0, 1, 2, 6, 12 and 48 h after the intraperitoneal administration of 0.9% saline containing either CP (200 mg/kg) or saline. The expression of IL-6 gene and IL-6 protein were detected using in situ hybridization histochemistry and immunocytochemistry, respectively.

Results: In situ hybridization histochemistry showed that IL-6 gene expression was significantly up-regulated in the bladder at 1 h in comparison to that at 0 h after CP administration. The levels of IL-6 gene expression peaked at 6 h after CP administration and then declined thereafter. In contrast, only a few IL-6 transcripts were expressed in the bladder but they remained unchanged following the administration of saline at all time points examined. The IL-6 transcripts were predominantly distributed in the perivascular area of the submucosal layers during CP-induced cystitis. Immunocytochemistry demonstrated IL-6 immunoreactivity in the spindle-shaped cells located in the vicinity of the dilated vessels of the submucosal layers during CP-induced cystitis.

Conclusion: IL-6 gene expression was up-regulated in the submucosal layer of the bladder and peaked at 6 h after CP administration, suggesting that the primary source of IL-6 may be fibroblasts in the bladder during CP-induced cystitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cyclophosphamide / toxicity
  • Cystitis / chemically induced
  • Cystitis / genetics*
  • Cystitis / metabolism
  • Disease Models, Animal
  • Immunohistochemistry
  • In Situ Hybridization / methods*
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / genetics*
  • Male
  • Mice
  • RNA, Messenger / genetics*
  • Up-Regulation*
  • Urinary Bladder / drug effects
  • Urinary Bladder / metabolism
  • Urinary Bladder / pathology*

Substances

  • Biomarkers
  • Interleukin-6
  • RNA, Messenger
  • Cyclophosphamide