Cytokine mRNA expression in the mucosa of treated coeliac patients after wheat peptide challenge.

Kontakou, M; Przemioslo, Robert; Sturgess, Richard; Limb, G. Astrid; Ellis, H. A.; Day, Phillip; Ciclitira, Paul J.

doi:10.1136/gut.37.1.52

Cited by 89 publications

(61 citation statements)

References 25 publications

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“…Moreover, relative to the proinflammatory cytokines, only low levels of mRNA for IFN-, IL-2, IL-4 and IL-5, cytokines which are normally associated with antigen-specific immune responses, were expressed in the patients and controls, either before or 4 h after gluten challenge. Although others noted an approximately two-fold increase in the number of cells in the lamina propria of the small intestine that express mRNA for IL-2, IFN-, TNF-and IL-6, 4 h following gliadin challenge [43], control subjects were not included in that report [43]. Further, it is possible that those increases reflected the migration of cells already expressing those cytokines to the site of gluten challenge in response to chemoattractant stimuli, rather than de novo induction of cytokine synthesis by antigen-specific T cells, since the numbers of cytokine-expressing cells, and not cytokine levels, were assessed.…”

Section: Discussionmentioning

confidence: 99%

Increased proinflammatory cytokine gene expression in the colonic mucosa of coeliac disease patients in the early period after gluten challenge

Chowers

Marsh

Grandpre

et al. 1997

Clinical and Experimental Immunology

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Activation of T cells in the intestinal mucosa in response to gluten exposure is thought to play a key role in the pathogenesis of coeliac disease. Moreover, the response of the rectal mucosa to gluten challenge has been considered a useful predictor of gluten sensitivity in coeliac disease. In the present study, we assessed early changes in the expression of proinflammatory cytokine genes and the T cell receptor (TCR) Vβ repertoire in the rectal mucosa of coeliac disease patients following experimental gluten challenge. Cytokine gene expression was assessed in rectal mucosal biopsies from coeliac disease subjects and controls before and after rectal gluten challenge using quantitative reverse transcription polymerase chain reaction analysis, and the TCR Vβ repertoire was characterized using a multiprobe RNase protection assay. Marked up‐regulation of expression of the C‐X‐C chemokine IL‐8, the proinflammatory cytokine IL‐1β, and the C‐C chemokine monocyte chemotactic protein‐1 occurred within 2–4 h of rectal gluten challenge in coeliac disease subjects, but not in controls. Furthermore, these changes occurred in the absence of parallel changes in the expressed repertoire of TCR Vβ genes in the rectal mucosa. Thus, an increased expression of proinflammatory cytokine genes precedes the expansion of antigen‐specific T cell populations in the early period following experimental exposure of the rectal mucosa of coeliac disease patients to gluten. These findings provide new insights into pathways that may be involved in the activation or reactivation of coeliac disease.

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Section: Discussionmentioning

confidence: 99%

Increased proinflammatory cytokine gene expression in the colonic mucosa of coeliac disease patients in the early period after gluten challenge

Chowers

Marsh

Grandpre

et al. 1997

Clinical and Experimental Immunology

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“…Since a correlation between the magnitude of villous atrophy and that of enterocyte apoptosis has been shown previously in untreated CD patients, 26 it is conceivable that, by degrading either interstitial ECM or basement membranes, 12 MMP-12 ultimately leads to the collapse of villous architecture and subsequent enterocyte shedding to the lumen. Furthermore, since MMP expression is highly dependent on cytokines 27,28 and gluten exposure in patients with CD rapidly elicits high levels of Th-1 cytokines, such as IFN-g, IL-2 and TNF-a, 13,14 we simultaneously determined the levels of IFN-g and TNF-a. Our results confirm a strong upregulation of IFN-g in active CD but not of TNF-a, the latter being in accordance with recent findings by Forsberg et al 29 who showed a suppression of TNF-a mRNA in this condition.…”

Section: Discussionmentioning

confidence: 99%

“…8,9 Even though a major role for MMPs in T-cell injury of the gut has already been shown in experimental models 10 and some MMPs have been found raised in CD, 11,12 a quantitative and wide assessment of MMPs in this pathological condition has never been performed. Similarly, the effect of the upregulation of T helper (Th)-1 cytokines 13,14 on the activation of these enzymes has never been investigated in celiac mucosa.…”

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confidence: 99%

Matrix metalloproteinase pattern in celiac duodenal mucosa

Ciccocioppo

Sabatino

Bauer

et al. 2005

Laboratory Investigation

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Matrix metalloproteinases (MMPs) are a family of endopeptidases playing a key role in tissue remodelling in both physiological and pathological conditions. Since little information is available about their role in celiac disease (CD), our aims were to quantify their expression/activity and to investigate their relation to proinflammatory cytokines in this condition. Duodenal biopsies from untreated, treated celiac patients and controls were used to quantify the expression of MMP-1, MMP-2, MMP-3, MMP-9, MMP-12, MMP-14, their inhibitor TIMP-1, IFN-c and TNF-a by using real-time reverse transcription-polymerase chain reaction and the gelatin/casein/elastin activities by gel zymography, and to isolate lamina propria mononuclear cells (LPMCs). These cells and myofibroblasts isolated from jejunal specimens were incubated in the absence or presence of IFN-c and TNF-a. MMP-1 and MMP-12 mRNA levels were significantly increased in active CD compared to treated (Po0.01 and Po0.0005, respectively) and normal mucosa (Po0.01 and Po0.0005, respectively), and this was paralleled by an upregulation of caseinolytic and elastolytic activities. Furthermore, MMP-12 levels significantly (Po0.05) correlated with those of IFN-c and the degree of villous flattening. MMP-2 turned out to be significantly (Po0.05) reduced in untreated and treated celiacs compared to controls. In active CD, transcripts of TIMP-1 were higher than in treated and controls (Po0.005 and Po0.05, respectively), such as those of IFN-c (Po0.05), whereas TNF-a levels were suppressed (P ¼ 0.0001). In physiological condition, myofibroblasts represent the main source of MMP-2, whereas LPMCs produce almost all MMPs only after cytokine stimulation. Conversely, cells isolated from active patients constitutively express MMPs without any increase after cytokine stimulation, while those from treated patients are in a resting condition. In conclusion, our results show the presence of a peculiar MMP pattern in active CD strongly dominated by MMP-12, correlating either with IFN-c or the degree of mucosal damage.

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“…CD is regarded as a T helper type 1 (Th1) disease because mucosal up-regulation of the interferon (IFN)-g pathway is seen [7][8][9]. We reported recently that mucosal up-regulation of IFN-g pathway remained elevated even 1 year after gluten-free diet (GFD), suggesting that activation of the Th1 response is triggered not only by dietary gliadin, but is associated more fundamentally with CD, being already present in potential CD and in treated CD [10].…”

Section: Introductionmentioning

confidence: 99%

Up-regulation of small intestinal interleukin-17 immunity in untreated coeliac disease but not in potential coeliac disease or in type 1 diabetes

Lahdenperä

Hölttä

Ruohtula

et al. 2012

Clinical and Experimental Immunology

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Cytokine mRNA expression in the mucosa of treated coeliac patients after wheat peptide challenge.

Abstract: This study investigated the presence of mRNA coding for interferon gamma

Cited by 89 publications

References 25 publications

Increased proinflammatory cytokine gene expression in the colonic mucosa of coeliac disease patients in the early period after gluten challenge

Increased proinflammatory cytokine gene expression in the colonic mucosa of coeliac disease patients in the early period after gluten challenge

Matrix metalloproteinase pattern in celiac duodenal mucosa

Up-regulation of small intestinal interleukin-17 immunity in untreated coeliac disease but not in potential coeliac disease or in type 1 diabetes

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