Corticosterone binding globulin regulation and thymus changes after thermal injury in mice

D’Elia, Michele; Patenaude, Johane; Hamelin, Claudine; Garrel, Dominique R.; Bernier, Jacques

doi:10.1152/ajpendo.00407.2004

Cited by 16 publications

(15 citation statements)

References 59 publications

(51 reference statements)

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“…Mice were subjected to a 20% total body surface area burn (TBSA) as described before (12). Briefly, mice were randomly assigned to a control or burn group, each containing eight animals.…”

Section: Animalsmentioning

confidence: 99%

“…Endogenous GC production is maximal following thermal injury, and the effect of this single event has already been associated with increased apoptosis seen in the thymus and spleen at days 1 and 2 postburn followed by a general recovery at day 5 postburn (12,21). GC responsiveness in T cells that either were selected or survived during these crucial first 5 days postburn has never been addressed.…”

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confidence: 99%

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T cells from burn-injured mice demonstrate a loss of sensitivity to glucocorticoids

D’Elia

Patenaude

Dupras

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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“…Mice were subjected to a 20% total body surface area burn (TBSA) as described before (12). Briefly, mice were randomly assigned to a control or burn group, each containing eight animals.…”

Section: Animalsmentioning

confidence: 99%

mentioning

confidence: 99%

T cells from burn-injured mice demonstrate a loss of sensitivity to glucocorticoids

D’Elia

Patenaude

Dupras

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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“…Mice were subjected to a 20% total body surface area burn as described previously (6). Briefly, mice were randomly assigned to a control or burn group, each containing eight animals.…”

Section: Animalsmentioning

confidence: 99%

“…One striking observation is thymic involution, which was characterized by the selective increased apoptosis of immature double-positive CD4 ϩ CD8 ϩ thymocytes while single-positive cells were unaffected. This transient event occurred as early as 24 h after a burn injury and was restricted to the first days, since normal thymus cellularity and thymocyte subpopulation numbers were observed in these mice at day 5 postburn injury (6). Administration of RU-486, a glucocorticoid receptor (GR) inhibitor, prevented burn-induced thymocyte apoptosis (21).…”

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confidence: 99%

“…Although the precise role of GC in the thymus remains unclear, major trauma results in increased GC levels associated with severe depletion of thymocytes by apoptosis (15). We have previously shown that CBG is mainly responsible for corticosterone (CORT) action after burn injury (6). Decreased CBG expression resulted in an increase of free CORT, which was associated with a decrease in total thymocyte numbers.…”

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Regulation of glucocorticoid sensitivity in thymocytes from burn-injured mice

D’Elia¹,

Patenaude²,

Bernier³

2009

American Journal of Physiology-Endocrinology and Metabolism

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Glucocorticoids (GC) are important steroid hormones that regulate metabolism, development, and the immune system. GC are produced continuously, and maximal levels are reached following stress-related stimuli. Previous studies have demonstrated that increased GC production following thermal injury was responsible for thymic involution. Although GC are mainly synthesized by the adrenal glands, there is increasing evidence that GC may also be produced in nonadrenal tissues. The thymus was reported to express steroidogenic enzymes and to release GC. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is predominantly a reductase in cells and is essential for the local reactivation of GC. Here, we report that increased GC-induced apoptosis in thymocytes from burn-injured mice is related to increased glucocorticoid receptor (GR) expression and 11β-HSD1 expression in thymocytes at day 1 postburn injury. In vitro, thymocytes were able to convert 11-dehydrocorticosterone (DHC) to corticosterone (CORT), which induced their apoptosis, and this was pharmacologically inhibited by 18β-glycyrrhetinic acid, a specific 11β-HSD inhibitor. Moreover, 11β-HSD1 expression was confirmed in the 267S3 thymoma-derived cell line, and its activity was responsible for greater sensitivity of these cells to CORT-induced apoptosis. Finally, proinflammatory cytokines [tumor necrosis factor-α, interleukin (IL)-1β, and IL-6] increased thymocyte sensitivity to DHC-induced apoptosis through a mechanism involving 11β-HSD1. Overall, we have shown that burn injury induced 11β-HSD1 expression in thymocytes, which led to a greater sensitivity of these cells to CORT-induced apoptosis. Increased expression of 11β-HSD1 and GR may play a role in intrathymic T cell development and can be major determinants of GC sensitivity after a trauma.

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Selective effect of burn injury on splenic CD11c+ dendritic cells and CD8α+CD4−CD11c+ dendritic cell subsets

Patenaude

D’Elia

Hamelin

et al. 2010

Cell. Mol. Life Sci.

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Burn injury causes an immunosuppression associated with suppressed adaptive immune function. Dendritic cells (DCs) are APCs for which signaling via their Toll-like receptors (TLRs) induces their maturation and activation, which is essential for the adaptive immune response. In this study, we examined if burn injury alters the TLR activity of splenic DCs. After injury, we noticed that DC functions were impaired, characterized by a suppressed capacity to prime naive T cells when triggering the TLR4 signaling cascade using specific ligands (LPS or rHSP60). The observed perturbations on LPS-primed DCs isolated from burned mice exhibited significantly diminished IL-12p40 production and enhanced IL-10 secretion-associated impairment in mitogen-activated protein kinase activation. Interestingly, we observed a decrease of TLR4/MD-2 expression on the CD8alpha(+) DC subset that persisted following LPS stimulation. The altered TLR4 expression on LPS-stimulated CD8alpha(+) DCs was associated with reduced capacity to produce IL-12 after stimulation. Our results suggested that TLR4 reactivity on DCs, especially CD8alpha(+) DCs, is disturbed after burn injury.

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Corticosterone binding globulin regulation and thymus changes after thermal injury in mice

Abstract: . Corticosterone binding globulin regulation and thymus changes after thermal injury in mice.

Cited by 16 publications

References 59 publications

T cells from burn-injured mice demonstrate a loss of sensitivity to glucocorticoids

T cells from burn-injured mice demonstrate a loss of sensitivity to glucocorticoids

Regulation of glucocorticoid sensitivity in thymocytes from burn-injured mice

Selective effect of burn injury on splenic CD11c+ dendritic cells and CD8α+CD4−CD11c+ dendritic cell subsets

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