Social Disruption Stress Exacerbates α-Galactosylceramide-Induced Hepatitis in Mice

Abstract

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 α-galactosylceramide (α-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 α-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. Conclusion: These findings demonstrated that, similar to electric foot-shock stress, social disruption stress exacerbated α-GalCer-induced hepatitis.

Social Stress Enhances Allergen-Induced Airway Inflammation in Mice and Inhibits Corticosteroid Responsiveness of Cytokine Production

“…Here we describe a unique murine model in which social stress and allergen exposure provides a platform to investigate the psycho-endocrine-immunological axis that regulates airway inflammation. Social disruption, a well characterized psychological stressor, has been used by our laboratory and others to assess the impact of a semi-natural stressor on immune function (35, 39–42). In this model a previously established social hierarchy of a stable cohort of younger male mice is disrupted by a large, aggressive male that confronts and repeatedly defeats the cage residents.…”

Early-Life Psychological Stress Exacerbates Adult Mouse Asthma via the Hypothalamus–Pituitary–Adrenal Axis

“…In animal experiments, a number of types of stress have been created and used in several disease models. In general, each stress is characterized according to a distributed ratio of physical and psychological burdens: for example, a physical burden is far more dominant in forced swimming, immobilization, and electrical FS stress (22,(29)(30)(31), whereas a psychological burden is created by social isolation stress, water avoidance stress, and social disruption stress (24,32,33). The communication box method, designed by Ogawa and Kuwahara (34), has Figure 8.…”

Interleukin-1 receptor type 1-deficient mice fail to develop social stress-associated glucocorticoid resistance in the spleen

“…Previous studies have demonstrated that repeated social stress in mice is associated with decreased GC sensitivity of immune cells and excessive inflammation Engler et al, 2005;Johnson et al, 2004;Merlot et al, 2004;Sonoda et al, 2005;Stark et al, 2001). For example, lipopolysaccharide (LPS)-stimulated splenocytes from mice that repeatedly experienced acute encounters with an aggressive conspecific exhibited considerably higher cell survival in the presence of corticosterone (CORT) and showed greatly enhanced production of pro-inflammatory cytokines compared to splenocyte cultures from non-stressed controls (Avitsur et al, 2005Merlot et al, 2004;Stark et al, 2001).…”