Corticosteroids impair intestinal epithelial wound repair mechanisms in vitro

Jung, Sandra; Fehr, Susanne; Harder-D'heureuse, Johanna; Wiedenmann, Bertram; Dignaß, Axel

doi:10.1016/s0016-5085(00)84327-9

Cited by 17 publications

(24 citation statements)

References 31 publications

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“…Bilateral ADX in rats led to partial atrophy and disorganization of the epithelium with increased villus apoptosis (13); however, it has also been noted that GC administration in vitro increases intestinal epithelial cell apop-tosis and inhibits cellular proliferation (21). Although intestinal epithelial cells produce cytokines that regulate apoptosis and cell proliferation of intestinal lymphocytes (50), our experiments demonstrate significantly higher lymphocyte counts for most phenotypes in ADX mice regardless of exercise condition.…”

Section: Discussionsupporting

confidence: 49%

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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Section: Discussionsupporting

confidence: 49%

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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“…Glucocorticoids are known to induce differentiation of the gut epithelium (Henning, 1981;Quaroni et al, 1999) and to suppress epithelial cell migration and proliferation in response to injury (present study and Jung et al, 2001). Indeed, CSs have also been reported to increase colonic damage in DSS-mice (Van Meeteren et al, 2000), although this effect was not observed in the present study.…”

Section: Glp-2 and Therapeutics In Colitis 351contrasting

confidence: 50%

Glucagon-Like Peptide-2 and Common Therapeutics in a Murine Model of Ulcerative Colitis

L’Heureux

Brubaker²

2003

J Pharmacol Exp Ther

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“…Monolayer wounding and measurement of epithelial cell resti tution IEC-6 cell restitution assays were performed using a modified version of a previously described technique [11,12] . IEC-6 cells were plated in six-well polystyrene plates (Costar) with normal growth medium and allowed to reach confluence.…”

Section: Determination Of Odc and C-myc Mrna Expression Profiles Usinmentioning

confidence: 99%

“…Secondly, epithelial cell proliferation takes place to replenish the decreased cell pool. Finally, maturation and differentiation of epithelial cells enable the epithelium to maintain its functional activities [12] . The initial mechanism contributing to rapid resealing of epithelial defects after mucosal injury is the migration of viable epithelial cells from the wound margin into the denuded area, which is a process that does not require cell proliferation [29] .…”

Section: Groupmentioning

confidence: 99%

Ganoderma lucidum polysaccharides reduce methotrexate-induced small intestinal damage in mice via induction of epithelial cell proliferation and migration

Chen

Lin

2011

Acta Pharmacol Sin

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Aim: To study the effects of Ganoderma lucidum polysaccharides (Gl-PS) on methotrexate (MTX)-induced small intestinal damage in mice and the underlying mechanisms. Methods: BALB/c mice were used for in vivo study. The mice were administered with Gl-PS (50, 100, or 200 mg/kg, ig) for 10 d, and injected with MTX (50 mg/kg, ip) on d 7 and 8 to induce intestinal damage, and then sacrificed on d 11 for morphological study and tissue malondialdehyde (MDA) and superoxide dismutase (SOD) measurements. Before sacrificing, blood samples were collected to analyze immunoglobulin A (IgA). Rat intestinal IEC-6 cells were used for in vitro study. Cell proliferation and migration were assessed using MTT method and an in vitro wounding model, respectively. Transforming growth factor β (TGFβ) protein expression was determined using ELISA assay. Ornithine decarboxylase (ODC) and c-Myc mRNA expression profiles were determined using RT-PCR. Results: MTX treatment caused severe mucosal damage, significantly increased small intestine MDA levels, and decreased SOD and serum IgA levels in BALB/c mice. Gl-PS (100 and 200 mg/kg) markedly reversed the MTX effects. In IEC-6 cells, Gl-PS (0.1, 1, and 10 μg/mL) significantly stimulated the cell proliferation. Furthermore, Gl-PS (10 μg/mL) significantly stimulated the cell migration. In addition, Gl-PS (10 and 20 μg/mL) significantly increased the expression of ODC and c-Myc mRNAs. However, Gl-PS (up to 20 μg/mL) had no effect on the expression of TGFβ protein. Conclusion:The results suggest that Gl-PS protects small intestine against MTX-induced injury via induction of epithelial cell proliferation and migration.

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Corticosteroids impair intestinal epithelial wound repair mechanisms in vitro

Cited by 17 publications

References 31 publications

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

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

Glucagon-Like Peptide-2 and Common Therapeutics in a Murine Model of Ulcerative Colitis

Ganoderma lucidum polysaccharides reduce methotrexate-induced small intestinal damage in mice via induction of epithelial cell proliferation and migration

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