Social disruption stress exacerbates alpha-galactosylceramide-induced hepatitis in mice.
OBJECTIVE
Psychosocial stress has been suggested as a possible aggravating factor in liver diseases, however, the underlying mechanism has yet to be clarified. Recently, our research revealed that electric foot-shock stress aggravated NK1.1 Ag(+) T cell-dependent alpha-galactosylceramide (alpha-GalCer)-induced hepatitis in mice via a mechanism mediated by endogenous glucocorticoids. In this study, we examined whether or not such aggravation could be applied to a psychosocially stressful situation, e.g. social disruption stress.


METHODS
Male wild-type C57BL/6 (B6) or B6 hepatitis virus type B surface antigen transgenic (HBs-tg) mice, a hepatitis B virus carrier mouse model, were exposed 3 times in 1 week to social disruption stress in which an 8-month-old aggressive male intruder was placed into their home cage (5 mice per group) for 2 h. Twelve hours after the final exposure to the stress, the wild-type and HBs-tg mice were intravenously injected with alpha-GalCer.


RESULTS
The stress-exposed wild-type mice exhibited significantly reduced thymus weight loss compared with the control animals. Moreover, this stress regimen led to a significant increase in serum alanine aminotransferase levels in both the wild-type and the HBs-tg mice, although the increase in the HBs-tg mice was higher than that in the wild-type mice.


CONCLUSIONS
These findings demonstrated that, similar to electric foot-shock stress, social disruption stress exacerbated alpha-GalCer-induced hepatitis.
Department of Psychosomatic Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Junko
J
Sonoda
Yoichi
Y
Chida
Nobuyuki
N
Sudo
Chiharu
C
Kubo
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology / Q000503:physiopathology*; D005434:Flow Cytometry; D005699:Galactosylceramides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013315:Stress, Psychological / Q000276:immunology / Q000503:physiopathology*; D013950:Thymus Gland / Q000473:pathology
D005699:Galactosylceramides; C493154:alpha-galactosylceramide; D000410:Alanine Transaminase