Suppression of T cell–mediated injury in human gut by interleukin 10: Role of matrix metalloproteinases

Pender, Sylvia L. F.; Breese, Emma J.; Günther, Ute; Howie, Duncan; Wathen, N. C.; Schuppan, Detlef; MacDonald, Thomas T.

doi:10.1016/s0016-5085(98)70136-2

Cited by 81 publications

(57 citation statements)

References 54 publications

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“…This model is supported by the results of other studies documenting the expression of Fas on epithelial cells and FasL by intestinal T cells in graft-vs-host disease (54,55). Previous reports have suggested that changes in epithelial cell structure and function can occur after exposing tissue to SEB (41,56). The ability of SEB to induce cytokines (42) as well as apoptosis in epithelial cells following exposure to SEB may contribute to the T cell-mediated pathology.…”

Section: Figuresupporting

confidence: 76%

Staphylococcal Enterotoxin B Stimulates Expansion of Autoreactive T Cells That Induce Apoptosis in Intestinal Epithelial Cells: Regulation of Autoreactive Responses by IL-10

Ito

Takaishi

Jin

et al. 2000

The Journal of Immunology

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T cell responses to self Ags and normal microbial flora are carefully regulated to prevent autoreactivity. Because IL-10-deficient mice develop colitis, and this response is triggered by luminal flora, we investigated whether IL-10 regulates the ability of microbial Ags to induce autoreactive T cells that could contribute to intestinal inflammation. T cells from wild-type mice were primed with staphylococcal enterotoxin B (SEB) in vitro, which induced an autoreactive proliferative response to syngeneic feeder cells. The cells were predominately CD3+ and CD4+. T cells from IL-10-deficient mice were constitutively autoreactive, and SEB priming enhanced this further. The autoreactive, proliferative response of T cells from wild-type mice was suppressed by IL-10 in the primary or secondary culture, and this effect was inhibited by neutralizing Abs to the IL-10R. To confirm that an autoreactive repertoire was expanded after SEB priming, we used CBA/J mice (Mls-1a) in which autoreactive T cells recognizing the endogenous viral superantigen are depleted (Vβ6, 7, 8.1 TCR-bearing cells). However, SEB rescued these autoreactive T cell repertoires. Adding anti-MHC class II Ab blocked the autoreactive response. SEB-primed splenic or colonic T cells also induced apoptosis in syngeneic intestinal epithelial cells that was blocked significantly by IL-10. Thus, microbial Ags have the potential to abrogate self tolerance by stimulating autoreactive T cells that become cytolytic to target cells. IL-10 plays a protective role in maintaining self tolerance after microbial stimulation by preventing the activation of T cells that contribute to epithelial cell damage.

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Section: Figuresupporting

confidence: 76%

Staphylococcal Enterotoxin B Stimulates Expansion of Autoreactive T Cells That Induce Apoptosis in Intestinal Epithelial Cells: Regulation of Autoreactive Responses by IL-10

Ito

Takaishi

Jin

et al. 2000

The Journal of Immunology

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“…IL-10 suppresses synthesis of proinflammatory cytokines such as IL-6 and TNF-α, and has been shown to reduce T-cell revitalization in in vitro and in vivo (Clerici et al, 1994;Pender et al, 1999;Schotte et al, 2004). In the present experiments, plasma IL-10 concentration increased more in the groups treated with A. victorialis extract than in the control group both at 2 and 5 h after LPS treatment (Fig.…”

Section: Plasma Il-10supporting

confidence: 52%

Anti-inflammatory Effects of Allium victorialis Extract in Lipopolysaccharide Exposed Rats and Raw 264.7 Cells

Lee¹

2014

Korean Journal of Plant Resources

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-This study examined the inflammatory reaction effects of Allium victorialis var. platyphyllum in vivo at the time of a lipopolysaccharide (LPS) shock in rats, and in vitro in cultured Raw 264.7 cells, with the aim of facilitating the development of a new anti-inflammatory medicine. Plasma concentrations of interleukin (IL)-1β, IL-6, tumor necrosis factor α (TNF-α), and IL-10 in rats peaked 5 h after LPS treatment in all experimental groups, with those of IL-1β, IL-6, and TNF-α being significantly lower in all animals treated with A. victorialis than in the control group at that time point. Conversely, the plasma concentration of IL-10 was higher in the rats treated with 300 ㎎/㎏ A. victorialis extract than in the control group at both 2 and 5 h after LPS treatment. Concentrations of IL-1β and IL-6 in the liver of rats treated with A. victorialis extract were significantly lower than those of the saline-treated control group. However, the liver concentrations of TNF-α and IL-10 did not vary significantly between the four animal groups. Similarly, concentrations of IL-1β, IL-6, and TNF-α obtained from cultured Raw 264.7 macrophages were lower in all of the A.-victorialis-extract-treated groups than in the control group. Although the concentration of IL-10 in the A.-victorialis-extract-treated groups tended to be greater than in the control group, the differences between groups were not statistically significant. Together the findings of this study suggest that A. victorialis var. platyphyllum contains functional substances that are involved in inflammatory reactions.

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“…Epithelial MMP-1 expression might be related to epithelial shedding. In an experimental inflammatory bowel disease model, the gut injury has been found to depend on MMP-3 production (17,40). However, our current results indicate that in graft-versus-host disease, MMPs do not function in tissue destruction, or at least destructive metalloenzymes differ from those considered to be important in inflammatory bowel disease.…”

Section: Discussionmentioning

confidence: 60%

Overexpression of Tissue Inhibitor of Metalloproteinases-3 in Intestinal and Cutaneous Lesions of Graft-versus-Host Disease

Salmela

Karjalainen–Lindsberg

Jeskanen

et al. 2003

Modern Pathology

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Matrix metalloproteinases (MMPs) have been implicated in the pathobiology of various T-cell-mediated inflammatory disorders of the intestine and skin. Their synthetic inhibitor has been shown to prevent lethal acute graft-versus-host disease in animal models. We intended to determine the expression of MMPs 1, 3, 7, 9, 10, 12, and 19 and tissue inhibitors of metalloproteinases (TIMPs) 1 and 3 in intestinal and cutaneous lesions of patients suffering from graft-versus-host disease after bone marrow transplantation. In situ hybridizations for MMPs 1, 3, 7, 10, and 12 as well as TIMPs 1 and 3 were performed using 35 S-labeled cRNA probes on intestinal (n ‫؍‬ 13) and cutaneous specimens (n ‫؍‬ 9) from patients with graft-versus-host disease. Immunohistochemical stainings were carried out to localize MMP-9, MMP-19, TIMP-3, and TGF-␤1 proteins, and TUNEL staining, to detect apoptotic cells. TIMP-3 mRNA and protein were detected in cutaneous lesions in areas with vacuolar degeneration of the basal epidermal layer in all skin samples, and they colocalized with apoptotic keratinocytes and partly with staining for TGF-␤. None of the MMPs examined were overexpressed in skin lesions. Signals for MMP-1 and MMP-3 mRNA was found in 10/13 and 5/13 intestinal biopsies, respectively. In the gut, MMP-19 -positive epithelial cells, particularly in the crypts, were found in 10/13 samples. Expression of MMPs 7, 9, 10, and 12 was absent or very low. TIMPs 1 and 3 were expressed by stromal cells in 12/13 and 10/13 gut samples, respectively. Whereas TIMP-1 was expressed particularly by subepithelial cells where epithelium had shed away, TIMP-3 was detected in deeper areas. We conclude that MMPs are differentially regulated in the skin and gut lesions of graft-versus-host disease. In agreement with previous data on cancer cells, TIMP-3, induced by TGF-␤1, may contribute to the apoptosis of keratinocytes in cutaneous graftversus-host disease lesions, leading to typical histopathological changes. We also conclude that MMPs play a less important role as effector molecules in intestinal graft-versus-host disease than in celiac or inflammatory bowel disease.

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Suppression of T cell–mediated injury in human gut by interleukin 10: Role of matrix metalloproteinases

Cited by 81 publications

References 54 publications

Staphylococcal Enterotoxin B Stimulates Expansion of Autoreactive T Cells That Induce Apoptosis in Intestinal Epithelial Cells: Regulation of Autoreactive Responses by IL-10

Staphylococcal Enterotoxin B Stimulates Expansion of Autoreactive T Cells That Induce Apoptosis in Intestinal Epithelial Cells: Regulation of Autoreactive Responses by IL-10

Anti-inflammatory Effects of Allium victorialis Extract in Lipopolysaccharide Exposed Rats and Raw 264.7 Cells

Overexpression of Tissue Inhibitor of Metalloproteinases-3 in Intestinal and Cutaneous Lesions of Graft-versus-Host Disease

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