Role of mucosal T-cell-generated cytokines in epithelial cell injury

Targan, Stephan R.; Deem, Richard L.; Shanahan, Fergus

doi:10.1007/bf02919744

Cited by 17 publications

(8 citation statements)

References 49 publications

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“…Inflammatory cells produce numerous soluble mediators; among them are cytokines, products of arachidonic acid metabolism, free oxygen radicals, and destructive enzymes such as matrix metalloproteinases. [26][27][28][29][30][31] As far as cytokines released by activated macrophages are concerned, the mechanisms by which they lead to mucosal injury are largely unknown. IL-1b causes an increase in metalloproteinases.…”

Section: Discussionmentioning

confidence: 99%

Tumor Necrosis Factor α Reduces Butyrate Oxidation In Vitro in Human Colonic Mucosa: A Link from Inflammatory Process to Mucosal Damage?

Nancey

Moussata

Graber

et al. 2005

Inflammatory Bowel Diseases

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TNFalpha at concentrations found in inflamed mucosa reduces butyrate oxidation in vitro in mucosa from healthy controls. This result is not caused by a cytotoxic effect of TNFalpha and is not balanced by an increased oxidation of glucose. Reduced butyrate oxidation results in a decreased energy supply to colonocytes and may explain, in part, mucosal damage occurring during attacks of inflammatory bowel disease.

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Section: Discussionmentioning

confidence: 99%

Tumor Necrosis Factor α Reduces Butyrate Oxidation In Vitro in Human Colonic Mucosa: A Link from Inflammatory Process to Mucosal Damage?

Nancey

Moussata

Graber

et al. 2005

Inflammatory Bowel Diseases

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“…Among all the different functions described for TNF-a (16,17), its role as a central regulator of inflammation and immunity is considered one of the most important (16,17). Indeed, recent investigations suggest a role for TNF-a in IBD (15,(18)(19)(20), and there are observations that provide support for the central role of TNF-a in the nonspecific indirect injury to epithelial cells as a mechanism of tissue injury in IBD (14,21). It is generally believed that activation of phospholipase A2 is an essential step in TNFa-mediated cytotoxicity (17), and TNF-a has been shown to stimulate both AA metabolism (22)(23)(24)(25)(26) and formation of PAF-acether (27) in several different cell types.…”

mentioning

confidence: 92%

“…Although there are differences between Crohn's disease and ulcerative colitis, a characteristic feature of IBD is the presence of activated macrophages and T lymphocytes in the intestinal mucosa (14,15). Both these cell types are known to produce the cytokine, tumor necrosis factor-a (TNF-a) (16).…”

mentioning

confidence: 99%

Tumor Necrosis Factor-α Potentiates Phospholipase A₂-Stimulated Release and Metabolism of Arachidonic Acid in Cultured Intestinal Epithelial Cells (INT 407)

Gustafson-Svärd

Tagesson

Boll

et al. 1993

Scandinavian Journal of Gastroenterology

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Tumor necrosis factor-alpha (TNF-alpha), a known pro-inflammatory cytokine, has been suggested to play a role in the pathogenesis of inflammatory bowel disease (IBD) by mediating damage to the intestinal epithelial cells. The present study demonstrates that TNF-alpha potentiates release and metabolism of 14C-labeled arachidonic acid (14C-AA) in cultured intestinal epithelial cells (INT 407). Although TNF-alpha on its own was but a weak stimulator of cellular 14C-AA turnover, it significantly potentiated the release of 14C-AA and 14C-labeled prostaglandin E2(14C-PGE2) after stimulation with three known phospholipase A2 activators: phospholipase. C from Clostridium perfringens, the calcium ionophore A23187, and the phorbol ester 4-beta-phorbol-12-myristate-13-acetate (PMA). The phospholipase A2 inhibitor quinacrine significantly reduced both AA and PGE2 release after combined stimulation with phospholipase C and TNF-alpha. In contrast to its effect on the AA turnover, TNF-alpha did not affect the phospholipase C-stimulated production of platelet-activating factor (PAF-acether). Taken together, these findings indicate that a) TNF-alpha potentiates phospholipase A2-stimulated AA release from cultured intestinal epithelial cells; b) TNF-alpha may stimulate phospholipase A2-dependent AA release without affecting the formation of PAF-acether and c) pretreatment with TNF-alpha potentiates the formation of PGE2 after stimulation with phospholipase A2 activators. In summary, the present investigation points to the possibility that TNF-alpha may stimulate intestinal epithelial cells to produce biologically active AA metabolites and that this stimulation may be modulated by components of the intestinal luminal content, like bacterial toxins.

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“…Studies using intestinal explants have shown that activation of T cells by specific antibody or mitogens resulted in crypt hyperplasia [9,10] and villous atrophy [9], suggesting a role for T cells or their secreted cytokines in these effects. Further, it has been suggested that the manifestations of villous atrophy are probably due to the T cell-derived cytokines interferon-gamma (IFN-) and tumour necrosis factor (TNF) [11], but the mechanisms involved in the induction of crypt cell hyperplasia are unknown.…”

Section: Introductionmentioning

confidence: 99%

IL-4 enhances IEC-6 intestinal epithelial cell proliferation yet has no effect on IL-6 secretion

McGee

Vitkus

1996

Clinical and Experimental Immunology

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SUMMARYIntestinal epithelial cells (IEC) form an important line of defence at the intestinal mucosa by providing a barrier to lumenal contents and also by their ability to secrete various inflammatory cytokines. Recently, several T cell-derived cytokines have been shown to regulate specific IEC functions. In this study, the effect of IL-4 on IEC proliferation and secretion of the inflammatory cytokine IL-6 was investigated using the non-transformed rat IEC-6 intestinal epithelial cell line. Recombinant rat (rr)IL-4 was found to enhance IEC-6 cell proliferation over 4 days of culture, and this enhancement was dose-dependent. Further studies using specific antibodies confirmed that IL-4 induced the effect and that the effect was not mediated by autocrine-produced transforming growth factor-alpha. However, IL-4 did not induce IL-6 secretion by the IEC-6 cells, nor did it alter IL-1¯-induced IL-6 secretion. These results indicate that T cells may be capable of regulating IEC proliferation via the secretion of IL-4 without altering the capacity of the IEC to function in the inflammatory response by secreting IL-6.

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Role of mucosal T-cell-generated cytokines in epithelial cell injury

Cited by 17 publications

References 49 publications

Tumor Necrosis Factor α Reduces Butyrate Oxidation In Vitro in Human Colonic Mucosa: A Link from Inflammatory Process to Mucosal Damage?

Tumor Necrosis Factor α Reduces Butyrate Oxidation In Vitro in Human Colonic Mucosa: A Link from Inflammatory Process to Mucosal Damage?

Tumor Necrosis Factor-α Potentiates Phospholipase A₂-Stimulated Release and Metabolism of Arachidonic Acid in Cultured Intestinal Epithelial Cells (INT 407)

IL-4 enhances IEC-6 intestinal epithelial cell proliferation yet has no effect on IL-6 secretion

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Role of mucosal T-cell-generated cytokines in epithelial cell injury

Cited by 17 publications

References 49 publications

Tumor Necrosis Factor α Reduces Butyrate Oxidation In Vitro in Human Colonic Mucosa: A Link from Inflammatory Process to Mucosal Damage?

Tumor Necrosis Factor α Reduces Butyrate Oxidation In Vitro in Human Colonic Mucosa: A Link from Inflammatory Process to Mucosal Damage?

Tumor Necrosis Factor-α Potentiates Phospholipase A2-Stimulated Release and Metabolism of Arachidonic Acid in Cultured Intestinal Epithelial Cells (INT 407)

IL-4 enhances IEC-6 intestinal epithelial cell proliferation yet has no effect on IL-6 secretion

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Tumor Necrosis Factor-α Potentiates Phospholipase A₂-Stimulated Release and Metabolism of Arachidonic Acid in Cultured Intestinal Epithelial Cells (INT 407)