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 language | English |
|---|---|
| Pages (from-to) | 105-114 |
| Number of pages | 10 |
| Journal | Reproduction |
| Volume | 150 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Aug 1 2015 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Obstetrics and Gynaecology
- Reproductive Medicine
- Embryology
- Endocrinology
- Cell Biology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Endogenous interleukin 18 regulates testicular germ cell apoptosis during endotoxemia
AU - Inoue, Taketo
AU - Aoyama-Ishikawa, Michiko
AU - Kamoshida, Shingo
AU - Nishino, Satoshi
AU - Sasano, Maki
AU - Oka, Nobuki
AU - Yamashita, Hayato
AU - Kai, Motoki
AU - Nakao, Atsunori
AU - Kotani, Joji
AU - Usami, Makoto
PY - 2015/8/1
Y1 - 2015/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84947437301&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84947437301&partnerID=8YFLogxK
U2 - 10.1530/REP-14-0427
DO - 10.1530/REP-14-0427
M3 - Article
C2 - 25934945
AN - SCOPUS:84947437301
VL - 150
SP - 105
EP - 114
JO - Reproduction
JF - Reproduction
SN - 1470-1626
IS - 2
ER -