Differential mucosal expression of Th17-related genes between the inflamed colon and ileum of patients with inflammatory bowel disease

Bogaert, Sara; Laukens, Debby; Peeters, Harald; Melis, Lode; Olievier, Kim; Boon, Nico; Verbruggen, Gust; Vandesompele, Jo; Elewaut, Dirk; Vos, Martine De

doi:10.1186/1471-2172-11-61

Cited by 56 publications

(45 citation statements)

References 47 publications

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“…The use of control tissues derived from the small intestine is valid in accordance with published studies identifying the colorectal junction as a primary site of O157 colonization in the large intestines of cattle (7,36). In addition, studies have reported the use of small or large intestinal tissues of healthy individuals as controls to determine relative increases in the expression of inflammatory cytokines in human patients with inflammatory bowel disease (4).…”

Section: Discussionsupporting

confidence: 50%

Correlating Levels of Type III Secretion and Secreted Proteins with Fecal Shedding of Escherichia coli O157:H7 in Cattle

et al. 2012

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The locus of enterocyte effacement (LEE) of Escherichia coli O157:H7 (O157) encodes a type III secretion system (T3SS) for secreting LEE-encoded and non-LEE-encoded virulence proteins that promote the adherence of O157 to intestinal epithelial cells and the persistence of this food-borne human pathogen in bovine intestines. In this study, we compared hha sepB and hha mutants of O157 for LEE transcription, T3SS activity, adherence to HEp-2 cells, persistence in bovine intestines, and the ability to induce changes in the expression of proinflammatory cytokines. LEE transcription was upregulated in the hha sepB and hha mutant strains compared to that in the wild-type strain, but the secretion of virulence proteins in the hha sepB mutant was severely compromised. This reduced secretion resulted in reduced adherence of the hha sepB mutant to Hep-2 cells, correlating with a significantly shorter duration and lower magnitude of fecal shedding in feces of weaned (n ‫؍‬ 4 per group) calves inoculated with this mutant strain. The levels of LEE transcription, T3SS activity, and adherence to HEp-2 cells were much lower in the wild-type strain than in the hha mutant, but no significant differences were observed in the duration or the magnitude of fecal shedding in calves inoculated with these strains. Examination of the rectoanal junction (RAJ) tissues from three groups of calves showed no adherent O157 bacteria and similar proinflammatory cytokine gene expression, irrespective of the inoculated strain, with the exception that interleukin-1␤ was upregulated in calves inoculated with the hha sepB mutant. These results indicate that the T3SS is essential for intestinal colonization and prolonged shedding, but increased secretion of virulence proteins did not enhance the duration and magnitude of fecal shedding of O157 in cattle or have any significant impact on the cytokine gene expression in RAJ tissue compared with that in small intestinal tissue from the same calves. Enterohemorrhagic Escherichia coli (EHEC) O157:H7 (referred to here as O157) causes a broad spectrum of diarrheal illnesses, including uncomplicated diarrhea, hemorrhagic colitis (HC), and hemolytic-uremic syndrome (HUS) (34). O157 infections are the major cause of acute renal failure in young children in the United States (34). Shiga toxins encoded by the stx 1 and stx 2 genes (52) are the major virulence factors responsible for the development of HC and HUS. Among ruminants, cattle are considered the major reservoir for O157 and animals colonized with these bacteria serve as major direct and indirect sources of this pathogen (28). O157 colonizes the large intestines of cattle, especially the cecum and tissues of the rectoanal junction (RAJ) (7, 37). Colonization requires intimate adherence of O157 bacteria to intestinal epithelial cells, a process that culminates in the formation of characteristic histopathological lesions called attaching and effacing (A/E) lesions. A/E histopathology results from the rearrangements of cytoskeletal elements of mucosal epithe...

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Section: Discussionsupporting

confidence: 50%

Correlating Levels of Type III Secretion and Secreted Proteins with Fecal Shedding of Escherichia coli O157:H7 in Cattle

et al. 2012

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“…A recent study revealed ileal IBD samples have increased expression of IL17A but unchanged expression of TGFB1, IL23A, STAT3, and the Th17 recruitment factors, whereas inflamed colonic samples have increased expression of all Th17 pathway-associated genes (55). Indeed, ileal IL17A expression was elevated in DSS-positive controls but was lowered by soy peptide supplementation.…”

Section: Discussionmentioning

confidence: 96%

Soy-Derived Di- and Tripeptides Alleviate Colon and Ileum Inflammation in Pigs with Dextran Sodium Sulfate-Induced Colitis3

Young

Ibuki

Nakamori

et al. 2012

The Journal of Nutrition

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We evaluated the antiinflammatory activity of soy-derived di- and tripeptides in a dextran sodium sulfate (DSS)-induced pig model of intestinal inflammation. In the DSS-positive control (POS) and DSS-positive with soy peptide treatment (SOY) groups (n = 6/group), DSS was administered to piglets via i.g. catheter for 5 d, followed by a 5-d administration of saline or soy-derived peptides, respectively. A negative control (NEG) group received saline in lieu of the DSS and soy peptides. The severity of inflammation was assessed by clinical signs, morphological and histological measurements, gut permeability, and neutrophil infiltration. Local production of TNF and IL6 were measured by ELISA, colonic and ileal inflammatory gene expression were assessed by real-time RT-PCR, and CD4+CD25+ lymphocyte populations were analyzed by flow cytometry. Crypt elongation and muscle thickness, d-mannitol gut permeation, colonic expression of the inflammatory mediators IFNG, IL1B, TNF, RORC, and IL17A as well as the FOXP3 T-regulatory transcription factor, and myeloperoxidase activity were lower (P < 0.05) in the SOY pigs than in POS pigs. Messenger RNA levels of ileal IFNG, TNF, IL12B, and IL17A were lower (P < 0.05) and FOXP3 expression was greater (P < 0.05) in SOY piglets than in the POS group. In the mesenteric lymph nodes, CD4+CD25+ T cells were higher (P < 0.05) in both the POS and SOY groups than in NEG controls. Soy-derived peptides exert antiinflammatory activity in vivo, suggesting their usefulness for the treatment of inflammatory disorders.

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“…Th17 cells and/or IL-17 are detected in CD patients [35-37,44-48]. However, the generation and functional relevance of Th17 cells remains poorly understood in CD patients.…”

Section: Discussionmentioning

confidence: 99%

Endogenous interleukin-10 constrains Th17 cells in patients with inflammatory bowel disease

et al. 2011

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BackgroundTh17 cells play a role in inflammation. Interleukin (IL)-10 is a potent anti-inflammatory cytokine. However, it is poorly understood whether and how endogenous IL-10 impacts the development of Th17 cells in human pathologies.Materials and methodsWe examined the relationship between IL-10 and Th17 cells in patients with Crohn's disease and in IL-10-deficient (IL-10-/-) mice. Th17 cells and dendritic cells (DCs) were defined by flow cytometry and evaluated by functional studies.ResultsWe detected elevated levels of IL-17 and Th17 cells in the intestinal mucosa of patients with Crohn's disease. Intestinal DCs from Crohn's patients produced more IL-1β than controls and were superior to blood DCs in Th17 induction through an IL-1-dependent mechanism. Furthermore, IL-17 levels were negatively associated with those of IL-10 and were positively associated those of IL-1β in intestinal mucosa. These data point toward an in vivo cellular and molecular link among endogenous IL-10, IL-1, and Th17 cells in patients with Crohn's disease. We further investigated this relationship in IL-10-/- mice. We observed a systemic increase in Th17 cells in IL-10-/- mice when compared to wild-type mice. Similar to the intestinal DCs in patients with Crohn's disease, murine IL-10-/- DCs produced more IL-1β than their wild-type counterparts and promoted Th17 cell development in an IL-1-dependent manner. Finally, in vivo blockade of IL-1 receptor signaling reduced Th17 cell accumulation and inflammation in a mouse model of chemically-induced colitis.ConclusionsEndogenous IL-10 constrains Th17 cell development through the control of IL-1 production by DCs, and reaffirms the crucial anti-inflammatory role of IL-10 in patients with chronic inflammation.

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Differential mucosal expression of Th17-related genes between the inflamed colon and ileum of patients with inflammatory bowel disease

Cited by 56 publications

References 47 publications

Correlating Levels of Type III Secretion and Secreted Proteins with Fecal Shedding of Escherichia coli O157:H7 in Cattle

Correlating Levels of Type III Secretion and Secreted Proteins with Fecal Shedding of Escherichia coli O157:H7 in Cattle

Soy-Derived Di- and Tripeptides Alleviate Colon and Ileum Inflammation in Pigs with Dextran Sodium Sulfate-Induced Colitis3

Endogenous interleukin-10 constrains Th17 cells in patients with inflammatory bowel disease

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