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


CONCLUSIONS
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.
Nishii
Hisae
H
Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Nomura
Masayoshi
M
Fujimoto
Naohiro
N
Matsumoto
Tetsuro
T
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003520:Cyclophosphamide / Q000633:toxicity; D003556:Cystitis / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D017403:In Situ Hybridization / Q000379:methods*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics*; D015854:Up-Regulation; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
D015415:Biomarkers; D015850:Interleukin-6; D012333:RNA, Messenger; D003520:Cyclophosphamide