Role of TNF-α in gut mucosal changes after severe burn

Spies, Marcus; Chappell, Vicky L.; Dasu, Mohan R.; Herndon, David N.; Thompson, James C.; Wolf, Steven E.

doi:10.1152/ajpgi.00149.2001

Cited by 55 publications

(35 citation statements)

References 21 publications

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“…Local intestinal TNF-␣ production may not change, despite significant increases in serum levels (58). Along these lines, administration of a neutralizing antibody to TNF-␣ was shown to prevent the increased enterocyte apoptosis following burn injury, despite the fact that no changes were identified in intestinal TNF-␣ mRNA expression (48). Although serum levels were not measured after SBR in the present study, no significant alterations in circulating levels of TNF-␣ were revealed in a previous report of rats undergoing a 70% SBR (31).…”

Section: Discussioncontrasting

confidence: 48%

Enterocyte apoptosis after enterectomy in mice is activated independent of the extrinsic death receptor pathway

Knott

O’Brien

Juno

et al. 2003

American Journal of Physiology-Gastrointestinal and Liver Physi

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. Enterocyte apoptosis after enterectomy SBR in mice is activated independent of the extrinsic death receptor pathway. Am J Physiol Gastrointest Liver Physiol 285: G404-G413, 2003. First published April 30, 2003 10.1152/ajpgi.00096.2003.-Intestinal adaptation following small bowel resection (SBR) is associated with greater rates of enterocyte apoptosis by unknown mechanism(s). Because postresection adaptation is associated with increased translocation of luminal bacteria, we sought to characterize the role for the extrinsic, death receptor pathway for the activation of enterocyte apoptosis after massive SBR. We first performed SBR or sham operations in mice, and the temporal expression of caspases 8, 9, and 3, death receptors tumor necrosis factor receptor-1 (TNFR 1) and Fas and corresponding ligands (TNF and Fas ligand) was determined in the remnant intestine at various postoperative time points. Ileal TNFR 1 and Fas expression were then measured after SBR in the setting of increased (waved-2 mice) or decreased (exogenous EGF administration) apoptosis. Finally, intestinal adaptation and apoptosis were recorded in the remnant ileum after SBR in TNFR 1-null and Fas-null mice. The expression of death receptor family proteins and caspases demonstrated only modest changes after SBR and did not correlate with the histological appearance of apoptosis. In the setting of accelerated apoptosis, TNFR 1 and Fas expression were paradoxically decreased. Apoptotic and adaptive responses were preserved in both TNFR 1-null and Fas-null mice. These results suggest that the mechanism for increased enterocyte apoptosis following massive SBR does not appear to involve the extrinsic, death receptor-mediated pathway.

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Section: Discussioncontrasting

confidence: 48%

Enterocyte apoptosis after enterectomy in mice is activated independent of the extrinsic death receptor pathway

Knott

O’Brien

Juno

et al. 2003

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…The significant decrease in small bowel weight following MTX treatment implies the presence of mucosal atrophy. 21 In accordance with this, the morphological appearance of the intestinal mucosa was characterized by epithelial desquamation and vacuolization, with an extensive loss of goblet cells. The inflamed intestines demonstrate the presence of oxidant injury, with elevated lipid peroxidation and depleted glutathione levels, which were accompanied by neutrophil accumulation, indicating a possible source of this oxidant injury.…”

Section: Discussionmentioning

confidence: 53%

Amelioration of methotrexate‐induced enteritis by melatonin in rats

Jahovic

Şener

Çevik

et al. 2004

Cell Biochemistry & Function

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The anti-tumour drug methotrexate (MTX) induces intestinal mucosa injury resulting in malabsorption and diarrhoea. The purpose of this study was to investigate whether exogenous melatonin could protect the gut from MTX-induced damage in rats. A single dose of MTX (20 mg kg(-1), i.p.) was followed by i.p. saline or melatonin injections (10 mg kg(-1), MTX + Mel) for the next 5 days. On the fifth day, intestinal transit was assessed using charcoal propagation. Rats were decapitated and small intestinal segments were fixed for light (LM) and scanning electron microscope (SEM) examinations. Other intestinal segments were stored to measure glutathione (GSH) and malondialdehyde (MDA) levels, myeloperoxidase (MPO) and ATPase activity. MTX led to loss of more than 10% of the initial body weight (p < 0.01). Conversely, weight loss was markedly less in the melatonin-treated MTX group (p < 0.05). Bowel motility was increased in MTX-treated rats, while the transit index in the MTX-Mel group was not different from the control group. MTX caused decreases in GSH levels and ATPase activity, with increases in MDA levels and MPO activity. These changes were reversed in MTX-Mel-treated rats (p < 0.05-p < 0.001). LM and SEM in the MTX group revealed desquamation of surface epithelium and glandular degeneration, while the epithelium was slightly damaged in the MTX-Mel group. In conclusion, the present study demonstrates that melatonin is capable of reversing MTX-induced intestinal dysfunctions, indicating that it may be beneficial in ameliorating the symptoms of chemotherapy-induced enteritis.

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“…Image capture and density analysis of bands was done with the SynGene gel documentation system (SynGene-Synoptics, Cambridge, UK), and the intensity of bands was expressed as the ratio of HSP70 to ␤-actin (36). Western blot analysis.…”

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confidence: 99%

Gene expression profiles and protein balance in skeletal muscle of burned children after β-adrenergic blockade

Herndon

Dasu

Wolfe

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

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Propranolol, a nonselective β-blocker, has been shown effective in hypermetabolic burn patients by decreasing cardiac work, protein catabolism, and lipolysis. This study investigates the effect of propranolol on gene and protein expression changes in skeletal muscle of burned children by use of high-density oligonucleotide arrays to establish the genetic profiles and stable isotope technique to quantitate protein synthesis. Thirty-seven children (mean age 9.7 ± 1.1 yr) were randomized into groups to receive placebo ( n = 23) or propranolol ( n = 14) titrated to reduce heart rate by 15%. Children had >40% total body surface area burns (mean 43 ± 5.6%). Protein net balance was determined by stable-isotope infusion technique. Total RNA from muscle biopsies was isolated, labeled, and cRNA hybridized to the HG-U95Av2 Affymetrix array. Mean net balance of protein synthesis and breakdown was –14.3 ± 12.9 nmol · min–1 · 100 ml leg volume–1 for placebo and +69.3 ± 34.9 nmol · min–1 · 100 ml leg volume–1 in the propranolol-treated children ( P = 0.012). Comparison of 12,000 genes in burned children receiving placebo showed increased expression of two genes with time, whereas children receiving propranolol showed increased expression of nine genes with a decrease in five genes. We conclude that burned children receiving propranolol showed a significant upregulation in genes involved in muscle metabolism and downregulation of an important enzyme involved in gluconeogenesis and insulin resistance compared with burned children receiving placebo. The upregulation of genes involved in muscle metabolism correlates well with the increase in net protein balance across the leg.

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Role of TNF-α in gut mucosal changes after severe burn

Cited by 55 publications

References 21 publications

Enterocyte apoptosis after enterectomy in mice is activated independent of the extrinsic death receptor pathway

Enterocyte apoptosis after enterectomy in mice is activated independent of the extrinsic death receptor pathway

Amelioration of methotrexate‐induced enteritis by melatonin in rats

Gene expression profiles and protein balance in skeletal muscle of burned children after β-adrenergic blockade

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