title: Electric foot shock stress-induced exacerbation of alpha-galactosylceramide-triggered apoptosis in mouse liver.
abstract: Recently, liver natural killer T (NKT) cells, which are specifically stimulated by alpha-galactosylceramide (alpha-GalCer), were found to play a critical role in intrahepatic immunity to several infections and certain hepatic disorders. However, the role of psychophysical stress on NKT cell-dependent liver injury induced by alpha-GalCer still remains to be elucidated. In this study, we employed inescapable electric foot shock as the mode of psychophysical stress and evaluated its effect on alpha-GalCer-induced hepatitis. Pre-exposure of 12 hours of foot shock stress before alpha-GalCer administration significantly enhanced alpha-GalCer-triggered increase in serum alanine aminotransferase levels, followed by increases in both liver caspase-3 activity and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive hepatocytes, thus indicating that the liver NKT cell-dependent apoptotic response was exacerbated by stress. Foot shock stress also significantly increased both the number of liver NKT cells and Fas expression levels on hepatocytes. Pretreatment with RU-486, a glucocorticoid (GC) receptor antagonist, completely reversed such stress-induced enhancement of the alpha-GalCer-triggered serum alanine aminotransferase and hepatocyte Fas antigen responses. In contrast, such a reversal effect was not found in the mice pretreated with naloxone, a micro-opioid receptor antagonist, which thus suggests that an elevation of endogenous GCs, but not beta-endorphin, as responsible for such stress-induced aggravation in mouse hepatitis models. In conclusion, foot shock stress-induced elevation of endogenous GCs exacerbates alpha-GalCer-initiated hepatic apoptosis through the expansion of liver NKT cells and the up-regulation of hepatocyte Fas antigen.
authors.affiliation: Department of Psychosomatic Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Chida
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Sudo
authors.forename: Junko
authors.initials: J
authors.lastname: Sonoda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sogawa
authors.forename: Chiharu
authors.initials: C
authors.lastname: Kubo
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D004597:Electroshock; D005699:Galactosylceramides; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016131:Lymphocyte Subsets; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D013315:Stress, Psychological / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D015854:Up-Regulation; D019014:fas Receptor / Q000378:metabolism
chemical_list: D005699:Galactosylceramides; D011965:Receptors, Glucocorticoid; D019014:fas Receptor; D000410:Alanine Transaminase