The immune system plays a central role for maintenance of human health. Repeat exposure to environmental xenobiotic have been shown in the past 20 years to impair the immune system. The immune response can be affected directly by toxic substances or indirectly by side effects on other physiological systems. Exposure to xenobiotic can induce a complex series of hormonal and metabolic changes that can modify the immune response. Thus, the immune and hormonal responses represent two system tightly associated. Studies of the mechanism by which an environmental xenobiotic can play a role as an endocrine disrupter at the level of the immune system or its cellular compartment is essential to understand and determine the risk assessment.
Our laboratory has two major aims on environmental toxics. One deals with the role of glucocorticoid release and his transporter on the immunosuppression mediated by xenobiotic exposure. The second aim deals on the characterization at the molecular level of the alteration of T cells signaling and activation following in vivo or in vitro exposure to xenobiotic.
In mammals, severe stress induce several changes in the endocrine system and is necessary for surviving. Overproduction of glucocorticoid following the activation of the hypothalamic-pituitary-adrenal axis is triggered by several hormones and modulated by cytokines. At the same time, corticosteroid-binding globulin (CBG), the main cortisol transporter, decreases dramatically. This glycoprotein is a member of the serine protease inhibitor family and has a stoichiometry of 1:1 for cortisol. In human, 90% of plasma cortisol is bound to CBG. CBG affinity for cortisol can be decreased by 10 fold following enzymatic cleavage by elastase, a polymorphonuclear enzyme. Since only cortisol unbound to CBG is biologically active, an increase of cortisol production or a decrease of his transporter can influence cortisol delivery in circulation. Moreover, lymphocytes have a specific high-affinity binding sites for CBG on cell membranes. Physiological variation of serum CBG can be modulated by some hormones (oestrogen, glucocorticoid) and by physiological stress (food restriction, inflammation).
Glucocorticoid plays a negative role on the immune function. An increase in plasma concentration of this hormone causes a defect in lymphocyte response and can lead to their elimination. Our laboratory studies the relation between environmental xenobiotic, the level of cortisol and CBG and immune response. Multiparametric study including determination of plasma concentration, binding capacity and gene expression of CBG are investigated in relation with the immune function. With these works, we can target some environmental contaminants and predict the risk for human health.
The second aim of our lab is to understand at the molecular level the mechanism(s) by which toxics exert their toxic effects on immune cells. Activation and signaling events in T cells line or purified cells following in vitro or in vivo exposure to xenobiotic are studied. Role of alteration in calcium homeostasis, tyrosine kinase signaling and regulatory transcription factors are focused. We also study the mechanism by which a toxic can induce cell death including necrosis and apoptosis. These studies on toxicants having a direct environmental concern can provide a better understanding on risk for human health.
Dr. Jacques Bernier received his B.Sc. and M.Sc. in biology from the Université du Québec a Montréal. He then obtained Ph.D. degree in cellular biology from the faculty of medicine of the Université de Sherbrooke. Following postdoctoral studies at the Institut de recherches cliniques de Montréal in molecular immunology, he joined the research center of Hôtel-Dieu de Montréal as independent researcher, working on the effect of burn injury on the immune response.
In 1997 Dr. Bernier became professor at INRS-Armand Frappier Institute while keeping an affiliation as an associate researcher with the Burn Research Center at the Hôtel-Dieu de Montréal.
His background is on the immunomodulation induced either by a pathogen, a physical stress or a xenobiotic. He is working on the role of endocrine disruptors on the immune function.
// 12 novembre 2018
Entretiens Jacques Cartier
// 30 mai 2013
Collation des grades 2012-2013
// 6 mai 2013
Bruno Johnson reçoit le prix Hans-Selye
Dans les médias
// 26 février 2016
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// 8 novembre 2013
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