A C-type lectin receptor pathway is responsible for the pathogenesis of acute cyclophosphamide-induced cystitis in mice

Takashi Dejima, Kensuke Shibata, Hisakata Yamada, ario takeuchi, Hiromitsu Hara, Masatoshi Eto, Seiji Naito, Yasunobu Yoshikai

Research output: Contribution to journalArticle

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Abstract

Hemorrhagic cystitis often arises after cyclophosphamide (CYP) administration. As yet, however, the mechanism involved in its pathogenesis is unknown. In this study, it was found that the Fc receptor γ chain (FcRγ)- caspase recruitment domain-containing protein 9 (CARD9)-dependent pathway rather than the myeloid differentiation primary response gene 88 (MyD88)-dependent pathway is involved in the pathogenesis of acute CYP-induced cystitis in mice. Rapid and transient production of interleukin (IL)-6 and IL-1β was detected in the bladder at 4 hr, preceding IL-23 and IL-17A production and an influx of neutrophils, which reached a peak at 24 hr after injection. As assessed by weight, edema and neutrophil infiltration, cystitis was significantly attenuated in CARD9 knockout (KO) and FcRγKO mice, this attenuation being accompanied by impaired production of IL-1β, IL-6, IL-23 and IL-17A. The major source of IL-17A is the vesical γδ T cell population: IL-17AKO, CδKO and Tyk2KO mice showed little IL-17A production and reduced neutrophil infiltration in the bladder after CYP injection. These results suggest that FcRγ-CARD9-dependent production of proinflammatory cytokines such as IL-1β, IL-6, and IL-23 and the subsequent activation of IL-17A-producing γδ T cells are at least partly involved in the pathogenesis of acute CYP-induced cystitis in mice.

Original languageEnglish
Pages (from-to)833-841
Number of pages9
JournalMICROBIOLOGY and IMMUNOLOGY
Volume57
Issue number12
DOIs
Publication statusPublished - Dec 1 2013

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C-Type Lectins
Cystitis
Interleukin-17
Cyclophosphamide
Interleukin-23
Interleukin-1
Interleukin-6
Urinary Bladder
Fc Receptors
Neutrophil Infiltration
T-Lymphocytes
Injections
Proteins
Interleukins
Knockout Mice
Edema
Neutrophils
Cytokines
Weights and Measures
Population

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Virology

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A C-type lectin receptor pathway is responsible for the pathogenesis of acute cyclophosphamide-induced cystitis in mice. / Dejima, Takashi; Shibata, Kensuke; Yamada, Hisakata; takeuchi, ario; Hara, Hiromitsu; Eto, Masatoshi; Naito, Seiji; Yoshikai, Yasunobu.

In: MICROBIOLOGY and IMMUNOLOGY, Vol. 57, No. 12, 01.12.2013, p. 833-841.

Research output: Contribution to journalArticle

Dejima, Takashi ; Shibata, Kensuke ; Yamada, Hisakata ; takeuchi, ario ; Hara, Hiromitsu ; Eto, Masatoshi ; Naito, Seiji ; Yoshikai, Yasunobu. / A C-type lectin receptor pathway is responsible for the pathogenesis of acute cyclophosphamide-induced cystitis in mice. In: MICROBIOLOGY and IMMUNOLOGY. 2013 ; Vol. 57, No. 12. pp. 833-841.
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