Endogenous interleukin 18 regulates testicular germ cell apoptosis during endotoxemia

Taketo Inoue, Michiko Aoyama-Ishikawa, Shingo Kamoshida, Satoshi Nishino, Maki Sasano, Nobuki Oka, Hayato Yamashita, Motoki Kai, Atsunori Nakao, Joji Kotani, Makoto Usami

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Orchitis (testicular swelling) often occurs during systemic inflammatory conditions, such as sepsis. Interleukin 18 (IL18) is a proinflammatory cytokine and is an apoptotic mediator during endotoxemia, but the role of IL18 in response to inflammation in the testes was unclear. WT and IL18 knockout (KO) mice were injected lipopolysaccharide (LPS) to induce endotoxemia and examined 12 and 48 h after LPS administration to model the acute and recovery phases of endotoxemia. Caspase activation was assessed using immunohistochemistry. Protein and mRNA expression were examined by western blot and quantitative real-time RT-PCR respectively. During the acute phase of endotoxemia, apoptosis (as indicated by caspase-3 cleavage) was increased in WT mice but not in IL18 KO mice. The death receptor-mediated and mitochondrial-mediated apoptotic pathways were both activated in the WT mice but not in the KO mice. During the recovery phase of endotoxemia, apoptosis was observed in the IL18 KO mice but not in the WT mice. Activation of the death-receptor mediated apoptotic pathway could be seen in the IL18 KO mice but not the WT mice. These results suggested that endogenous IL18 induces germ cell apoptosis via death receptor mediated- and mitochondrial-mediated pathways during the acute phase of endotoxemia and suppresses germ cell apoptosis via death-receptor mediated pathways during recovery from endotoxemia. Taken together, IL18 could be a new therapeutic target to prevent orchitis during endotoxemia.

Original languageEnglish
Pages (from-to)105-114
Number of pages10
JournalReproduction
Volume150
Issue number2
DOIs
Publication statusPublished - Aug 1 2015
Externally publishedYes

Fingerprint

Interleukin-18
Endotoxemia
Germ Cells
Apoptosis
Death Domain Receptors
Knockout Mice
Orchitis
Lipopolysaccharides
Caspases
Caspase 3
Testis
Real-Time Polymerase Chain Reaction
Sepsis
Western Blotting
Immunohistochemistry
Cytokines
Inflammation
Messenger RNA

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Reproductive Medicine
  • Embryology
  • Endocrinology
  • Cell Biology

Cite this

Inoue, T., Aoyama-Ishikawa, M., Kamoshida, S., Nishino, S., Sasano, M., Oka, N., ... Usami, M. (2015). Endogenous interleukin 18 regulates testicular germ cell apoptosis during endotoxemia. Reproduction, 150(2), 105-114. https://doi.org/10.1530/REP-14-0427

Endogenous interleukin 18 regulates testicular germ cell apoptosis during endotoxemia. / Inoue, Taketo; Aoyama-Ishikawa, Michiko; Kamoshida, Shingo; Nishino, Satoshi; Sasano, Maki; Oka, Nobuki; Yamashita, Hayato; Kai, Motoki; Nakao, Atsunori; Kotani, Joji; Usami, Makoto.

In: Reproduction, Vol. 150, No. 2, 01.08.2015, p. 105-114.

Research output: Contribution to journalArticle

Inoue, T, Aoyama-Ishikawa, M, Kamoshida, S, Nishino, S, Sasano, M, Oka, N, Yamashita, H, Kai, M, Nakao, A, Kotani, J & Usami, M 2015, 'Endogenous interleukin 18 regulates testicular germ cell apoptosis during endotoxemia', Reproduction, vol. 150, no. 2, pp. 105-114. https://doi.org/10.1530/REP-14-0427
Inoue T, Aoyama-Ishikawa M, Kamoshida S, Nishino S, Sasano M, Oka N et al. Endogenous interleukin 18 regulates testicular germ cell apoptosis during endotoxemia. Reproduction. 2015 Aug 1;150(2):105-114. https://doi.org/10.1530/REP-14-0427
Inoue, Taketo ; Aoyama-Ishikawa, Michiko ; Kamoshida, Shingo ; Nishino, Satoshi ; Sasano, Maki ; Oka, Nobuki ; Yamashita, Hayato ; Kai, Motoki ; Nakao, Atsunori ; Kotani, Joji ; Usami, Makoto. / Endogenous interleukin 18 regulates testicular germ cell apoptosis during endotoxemia. In: Reproduction. 2015 ; Vol. 150, No. 2. pp. 105-114.
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