TY - JOUR
T1 - Voluntary Wheel Running Reduces the Acute Inflammatory Response to Liver Carcinogen in a Sex-specific Manner
AU - Bay, M L
AU - Gehl, Julie
AU - Pedersen, Bente Klarlund
AU - Hojman, Pernille
N1 - ©2017 American Association for Cancer Research.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Inflammation contributes to the development of cancer, yet acute inflammatory responses are also needed to eradicate tumor-igenic cells and activate adaptive immune responses to combat cancer. Physical exercise has direct immunomodulatory effects, and in line with this, exercise has been demonstrated to inhibit tumor growth, including diethylnitrosamine-(DEN)-induced hepatocarcinoma. Having observed a sex-dependent development of DEN-induced hepatocarcinoma, we aimed to evaluate the effect of exercise and sex on the acute inflammatory response to DEN. Thus, we randomized male and female mice to cages with or without running wheels for 6 weeks, whereafter DEN was administered and the inflammatory response was evaluated for up to 96 hours. DEN administration caused marked acute inflammatory responses in female mice with weight loss, reduced food intake, release of liver enzymes, and increased systemic levels of IL6. Moreover, DEN caused increased hepatic expression of cytokines, immune cell markers, and components of the toll-like receptor signaling pathway. In male mice, DEN administration provoked similar physiologic effects with weight loss and reduced food intake, but less systemic and hepatic acute inflammation, which was associated with a higher baseline expression of the detoxifying enzyme glutathione S-transferase and lower expression of ERa in male mice. Voluntary wheel running attenuated systemic and hepatic inflammation, in particular in the female mice, and shifted the peak time of the inflammatory response. In conclusion, DEN elicited an acute inflammatory response in particular in female mice, and this response was attenuated by prior exercise.
AB - Inflammation contributes to the development of cancer, yet acute inflammatory responses are also needed to eradicate tumor-igenic cells and activate adaptive immune responses to combat cancer. Physical exercise has direct immunomodulatory effects, and in line with this, exercise has been demonstrated to inhibit tumor growth, including diethylnitrosamine-(DEN)-induced hepatocarcinoma. Having observed a sex-dependent development of DEN-induced hepatocarcinoma, we aimed to evaluate the effect of exercise and sex on the acute inflammatory response to DEN. Thus, we randomized male and female mice to cages with or without running wheels for 6 weeks, whereafter DEN was administered and the inflammatory response was evaluated for up to 96 hours. DEN administration caused marked acute inflammatory responses in female mice with weight loss, reduced food intake, release of liver enzymes, and increased systemic levels of IL6. Moreover, DEN caused increased hepatic expression of cytokines, immune cell markers, and components of the toll-like receptor signaling pathway. In male mice, DEN administration provoked similar physiologic effects with weight loss and reduced food intake, but less systemic and hepatic acute inflammation, which was associated with a higher baseline expression of the detoxifying enzyme glutathione S-transferase and lower expression of ERa in male mice. Voluntary wheel running attenuated systemic and hepatic inflammation, in particular in the female mice, and shifted the peak time of the inflammatory response. In conclusion, DEN elicited an acute inflammatory response in particular in female mice, and this response was attenuated by prior exercise.
U2 - 10.1158/1940-6207.capr-17-0075
DO - 10.1158/1940-6207.capr-17-0075
M3 - Journal article
C2 - 28951483
SN - 1940-6207
VL - 10
SP - 719
EP - 728
JO - Cancer Prevention Research
JF - Cancer Prevention Research
IS - 12
ER -
