Restraint stress-induced thymic involution and cell apoptosis are dependent on endogenous glucocorticoids

Tarcic, Nora; Ovadia, Haim; Weiss, David; Weidenfeld, Joseph

doi:10.1016/s0165-5728(97)00186-0

Cited by 130 publications

(91 citation statements)

References 51 publications

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“…These cytokines stimulate the hypothalamicpituitary-adrenal (HPA) axis and induce the release of glucocorticoids (GC) both in vivo [24] and in vitro [25]. GC have been shown to be one of the main mediators of DP thymocyte-induced apoptosis, and thymic involution does not occur in adrenalectomized animals [26,27]. The mobilization of immune cells to the site of an extensive inflammation such as colitis causes stress to the organism resulting in the production of glucocorticoids.…”

Section: Discussionmentioning

confidence: 99%

Dextran Sulfate Sodium‐induced Colitis Generates a Transient Thymic Involution – Impact on Thymocyte Subsets

et al. 2007

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One of the most widely used animal models for inflammatory bowel disease (IBD) is the dextran sulfate sodium (DSS)‐induced colitis. We have previously reported that 5 days administration of DSS in C57Bl/6J mice induces a colonic inflammation that progresses into chronicity after DSS removal, whereas in BALB/cJ mice the inflammation resolves within 4 weeks post‐DSS. Here we show that both thymic size and thymocyte numbers dramatically decreased in the acute phase of inflammation in C57Bl/6 mice, 7 days after DSS withdrawal. Mature, CD4+ and CD8+ single positive (SP) CD69lo CD62Lhi thymocytes were enriched in these mice, accompanied by a major decrease in the number of immature double positive (DP) thymocytes. However, the different maturation stages within the DP thymocyte subset were unchanged between healthy and inflamed C57Bl/6J mice. Interestingly, as the inflammation progressed into the chronic phase, the thymus recovered and 2 weeks after the acute inflammatory phase all the thymic parameters investigated in this study were restored to normal. In contrast, BALB/cJ mice only develop mild thymic alterations. Nevertheless, we found that within the double negative (DN) thymocytes an increased frequency and also total numbers of CD44+ CD25− (DN1) cells correlated with the severety of colitis, and that the frequency of CD44− CD25− (DN4) thymocytes decreased proportionally in the acute phase in BALB/cJ mice. Our observations suggest that the thymic effects are intimately connected to the intestinal inflammatory response in colitis regardless of the inflammatory stimuli.

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Section: Discussionmentioning

confidence: 99%

Dextran Sulfate Sodium‐induced Colitis Generates a Transient Thymic Involution – Impact on Thymocyte Subsets

et al. 2007

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“…It has been shown that glucocorticoidinduced lymphoid organ atrophy results, in part, from lymphocyte apoptosis [20]. Furthermore, subsets of immune cells are known to respond differently to glucocorticoid [21].…”

Section: Discussionmentioning

confidence: 99%

Differential response of murine CD4⁺CD25⁺ and CD4⁺CD25^– T cells to dexamethasone‐induced cell death

et al. 2004

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“…In vitro exposure to GCs induces thymocyte apoptosis (18,26), and blocking GC receptors, inhibiting GC biosynthesis, and ADX reduce lymphocyte cell death (6,15,43). Furthermore, surgical removal of the adrenal glands is associated with less DNA fragmentation and lower nitric oxide production of splenic macrophages (5).…”

Section: Discussionmentioning

confidence: 99%

Adrenalectomy in mice does not prevent loss of intestinal lymphocytes after exercise

Hoffman‐Goetz

Quadrilatero

Boudreau

et al. 2004

Journal of Applied Physiology

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Exhaustive exercise is associated with an increase in circulating glucocorticoids (GCs), lymphocyte apoptosis, and a reduction in intestinal lymphocyte number. The present study examined the role of GCs on the numerical changes seen in intestinal lymphocytes after exercise. Female C57BL/6 mice were bilaterally adrenalectomized (ADX; n ϭ 18) or given sham surgery (Sham; n ϭ 18) and assigned to one of three exercise conditions: treadmill running (28 m/min, 90 min, 2°slope) and killed immediately or after 24 h recovery, or not exercised and killed immediately after 90-min exposure to the treadmill environment. Lymphocytes were isolated from the intestines with CD45 ϩ cells collected by positive selection using magnetic bead separation columns, and lymphocyte subpopulations were analyzed by flow cytometry for CD45 ϩ , CD3␣␤ ϩ , CD3␥␦ ϩ , CD8␤ ϩ , CD8␣ ϩ , CD4 ϩ , and NK ϩ phenotypic markers. ADX mice had significantly more intestinal CD45 ϩ leukocytes (P Ͻ 0.05) and CD3␣␤ ϩ (P Ͻ 0.05), CD3␥␦ ϩ (P Ͻ 0.01), CD8␣ ϩ (P Ͻ 0.001), and NK ϩ (P Ͻ 0.05) intestinal lymphocytes than Sham mice. There was a significant effect of exercise condition on total intestinal CD45 ϩ leukocytes (P Ͻ 0.01) and CD3␣␤ ϩ (P Ͻ 0.05), CD8␣ ϩ (P Ͻ 0.001), and CD4 ϩ (P Ͻ 0.05) intestinal lymphocytes, with fewer cells at 24 h postexercise compared with the other treatment conditions. There were no surgical ϫ exercise interaction effects on the CD3 and CD8 phenotype numbers. Plasma corticosterone was virtually nil in ADX mice regardless of exercise condition but was significantly elevated in Sham mice immediately postexercise (P Ͻ 0.001). The data indicate that ADX does not prevent the loss of lymphocytes from the intestinal mucosa 24 h after strenuous exercise and GCs are not directly causal in the leukopenia of exercise. treadmill running; adrenal glands; glucocorticoids NUMEROUS STUDIES HAVE SHOWN that acute exercise is associated with induction of apoptosis or programmed cell death and loss of lymphocytes from blood, thymus, and spleen in humans and laboratory animals (9,20,28,29). Lymphocyte loss and/or apoptosis have been observed in other situations characterized by extreme physiological stress, including burn injury (15), electrical shock (48), and chronic restraint stress (42), and may reflect release of stress hormones, in particular glucocorticoids (GCs). GCs trigger apoptosis in lymphocytes by acting on an intracellular pathway via the mitochondria (2), which results in the accumulation of mitochondrial derived cytochrome c within the cytosol, loss of mitochondrial membrane integrity, externalization of phosphatidylserine at cell membranes, and DNA fragmentation (27,45).The intestinal intraepithelial lymphocytes (IELs) are a unique population of T cells that function as a first line of defense against exogenous pathogens, many of which develop independently of the thymus gland [i.e., T cells with the ␥␦ form of the T cell receptor (TCR)] (35). IELs play an important role in protection from epithelial tumor cells through their function a...

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Restraint stress-induced thymic involution and cell apoptosis are dependent on endogenous glucocorticoids

Cited by 130 publications

References 51 publications

Dextran Sulfate Sodium‐induced Colitis Generates a Transient Thymic Involution – Impact on Thymocyte Subsets

Dextran Sulfate Sodium‐induced Colitis Generates a Transient Thymic Involution – Impact on Thymocyte Subsets

Differential response of murine CD4⁺CD25⁺ and CD4⁺CD25^– T cells to dexamethasone‐induced cell death

Adrenalectomy in mice does not prevent loss of intestinal lymphocytes after exercise

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Restraint stress-induced thymic involution and cell apoptosis are dependent on endogenous glucocorticoids

Cited by 130 publications

References 51 publications

Dextran Sulfate Sodium‐induced Colitis Generates a Transient Thymic Involution – Impact on Thymocyte Subsets

Dextran Sulfate Sodium‐induced Colitis Generates a Transient Thymic Involution – Impact on Thymocyte Subsets

Differential response of murine CD4+CD25+ and CD4+CD25– T cells to dexamethasone‐induced cell death

Adrenalectomy in mice does not prevent loss of intestinal lymphocytes after exercise

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Differential response of murine CD4⁺CD25⁺ and CD4⁺CD25^– T cells to dexamethasone‐induced cell death