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 journalArticlepeer-review

7 Citations (Scopus)


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
Issue number2
Publication statusPublished - Aug 1 2015
Externally publishedYes

ASJC Scopus subject areas

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


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