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Up‐regulation of interleukin‐6 gene expression in cyclophosphamide‐induced cystitis in mice: An in situ hybridization histochemical study
Author(s) -
NISHII HISAE,
NOMURA MASAYOSHI,
FUJIMOTO NAOHIRO,
MATSUMOTO TETSURO
Publication year - 2006
Publication title -
international journal of urology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.172
H-Index - 67
eISSN - 1442-2042
pISSN - 0919-8172
DOI - 10.1111/j.1442-2042.2006.01536.x
Subject(s) - in situ hybridization , immunocytochemistry , immunohistochemistry , gene expression , medicine , saline , pathology , cyclophosphamide , microbiology and biotechnology , urinary bladder , gene , endocrinology , biology , biochemistry , chemotherapy
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.