Intestinal Trefoil Factor Induces Decay-Accelerating Factor Expression and Enhances the Protective Activities Against Complement Activation in Intestinal Epithelial Cells

Andoh, Akira; Kinoshita, Koichi; Rosenberg, Ian M.; Podolsky, Daniel K.

doi:10.4049/jimmunol.167.7.3887

Cited by 56 publications

(51 citation statements)

References 45 publications

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“…Peptidoglycan motifs that are recognized by NOD1 are delivered into host cells via the cag secretion system, and an important signaling event mediated by NOD1 is activation of NF-B (24). However, although other investigators have shown that DAF regulation is responsive to NF-B activation by pro-inflammatory stimuli (43,50), our data demonstrate that NF-B activation is not necessary for DAF induction by H. pylori. Another intriguing hypothesis based on a recent investigation (51) is that binding of CagL to cell surface ␣ 5 ␤ 1 integrins can alter local membrane dynamics and eventuate in the assembly of focal adhesions that trigger integrin signaling cascades (52).…”

Section: Discussioncontrasting

confidence: 46%

“…The daf promoter contains a B response element, and activation of NF-B leads to the up-regulation of DAF in response to proinflammatory stimuli (41)(42)(43)(44). To define the role of NF-B in H. pylori-induced DAF expression, MKN28 cells were transiently transfected with constructs that express either a dominant-negative IB␣ or dominant-negative IB kinase ␤ as well as a NF-B-responsive luciferase reporter construct.…”

Section: H Pylori Induction Of Daf Occurs Via a Nf-b-independentmentioning

confidence: 99%

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Regulation of the Helicobacter pylori Cellular Receptor Decay-accelerating Factor

O’Brien

Romero–Gallo

Schneider³

et al. 2008

Journal of Biological Chemistry

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Chronic gastritis induced by Helicobacter pylori is the strongest known risk factor for peptic ulceration and distal gastric cancer, and adherence of H. pylori to gastric epithelial cells is critical for induction of inflammation. One H. pylori constituent that increases disease risk is the cag pathogenicity island, which encodes a secretion system that translocates bacterial effector molecules into host cells. Decay-accelerating factor (DAF) is a cellular receptor for H. pylori and a mediator of the inflammatory response to this pathogen. H. pylori induces DAF expression in human gastric epithelial cells; therefore, we sought to define the mechanism by which H. pylori up-regulates DAF and to extend these findings into a murine model of H. pylori-induced injury. Co-culture of MKN28 gastric epithelial cells with the wild-type H. pylori cag ؉ strain J166 induced transcriptional expression of DAF, which was attenuated by disruption of a structural component of the cag secretion system (cagE). H. pylori-induced expression of DAF was dependent upon activation of the p38 mitogen-activated protein kinase pathway but not NF-B. Hypergastrinemic INS-GAS mice infected with wildtype H. pylori demonstrated significantly increased DAF expression in gastric epithelium versus uninfected controls or mice infected with an H. pylori cagE ؊ isogenic mutant strain. These results indicate that H. pylori cag ؉ strains induce up-regulation of a cognate cellular receptor in vitro and in vivo in a cag-dependent manner, representing the first evidence of regulation of an H. pylori host receptor by the cag pathogenicity island.

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Section: Discussioncontrasting

confidence: 46%

Section: H Pylori Induction Of Daf Occurs Via a Nf-b-independentmentioning

confidence: 99%

Regulation of the Helicobacter pylori Cellular Receptor Decay-accelerating Factor

O’Brien

Romero–Gallo

Schneider³

et al. 2008

Journal of Biological Chemistry

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“…At the same time, gut epithelial cells themselves can synthesize and secrete complement locally (34 -36). As indicated (see Introduction), evidence for the involvement of complement activation has been obtained in different forms of IBD as well as gastritis (19,37,38). In all of these diseases, C3b deposition can be detected on luminal epithelial cells.…”

Section: Discussionmentioning

confidence: 90%

“…In humans, under constitutive conditions, DAF is expressed sporadically on the luminal surface but, as indicated (see Introduction), its expression is up-regulated during inflammation (16,38,40). Despite these and the above observations, the importance of intrinsic complement regulatory activity in the GI tract has received little study.…”

Section: Discussionmentioning

confidence: 94%

Decay-Accelerating Factor Deficiency Increases Susceptibility to Dextran Sulfate Sodium-Induced Colitis: Role for Complement in Inflammatory Bowel Disease

Lin¹,

Spencer

Hatala³

et al. 2004

The Journal of Immunology

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Decay-accelerating factor (DAF or CD55) is expressed on colonic epithelial cells but its function in the mucosa is unknown. In humans, a proportion of DAF-deficient (Cromer INAB) patients develop inflammatory bowel disease (IBD). To evaluate how DAF deficiency may contribute to gut inflammation and thus could play a role in IBD pathogenesis, we compared the severity of dextran sulfate sodium-induced colitis in Daf1 gene-targeted and control mice. Seven days after consuming 3% dextran sulfate sodium in their drinking water, Daf1−/− mice suffered markedly greater weight loss (−24.7 ± 7.5% vs −14.2% ± 4.9%), exhibited uniformly bloody diarrhea as compared with soft stool in control mice, developed shortened colons, and had larger spleens. Histological examination of distal colons showed massively increased neutrophilic and mononuclear cell infiltration, greater epithelial cell destruction, and increased ulcerations. Cytokine production in organ cultures of colonic explants showed increased levels of IL-12 and IL-6. Fourteen days after switching back to regular water, in contrast to the Daf1+/+ controls which showed little stool abnormality, all Daf1−/− mice continued to have diarrhea. Organ culture cytokine measurements at this time point, i.e., the end of the recovery phase, showed markedly increased levels of IL-10 (6-fold), IL-12 (4-fold), and IL-6 (2-fold), as well as TNF-α (>10-fold) compared with the controls. Our findings argue that, as shown for IL-10 in IL-10−/− mice and IL-2 in IL-2−/− mice, DAF control of complement additionally is important in regulating gut homeostasis and consequently its activity may participate in protecting against IBD.

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“…The representation of components of complement system during the course of mucosal damage has been described in several previous studies, [39][40][41][42] but it is still limited. In the present study, we provide evidence that complement…”

Section: Discussionmentioning

confidence: 99%

Blockade of complement activation product C5a activity using specific antibody attenuates intestinal damage in trinitrobenzene sulfonic acid induced model of colitis

Chen¹,

Yang

Gao

et al. 2011

Laboratory Investigation

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Complement represents a chief component of innate immunity in host defense. However, excessive complement activation has been involved in the pathogenesis of inflammatory diseases. In this study, we investigated the contribution of complement to intestinal pathology of patients and rodents with inflammatory bowel disease. The expression of complement effectors (C3a and C3) was increased remarkably in inflamed colons of IBD patients compared with those of normal counterparts. In accordance with this, the sustained activation of complement in serum and colon (including elevated C3a and C5a levels, enhanced hemolytic activity, downregulated expression of C5a receptors) was observed, following the establishment of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis, which peaked at 24 h. Mice pretreated with neutralizing anti-C5a antibodies (À2, 0, and 2 days after TNBS instillation) had significantly reduced weight loss and improved macroscopic/microscopic scores, comparable to the efficacy of prednisolone treatment. Strikingly, treatment with anti-C5a at 24 h after TNBS instillation showed remarkable therapeutic effects, whereas prednisolone did not. The efficacy of anti-C5a administration was associated with decreased release of proinflammatory chemokines and cytokines, inhibition of infiltration of neutrophils into colons, and enhanced Th2 response. These findings suggest a disease-promoting role of complement, particular C5a, in the pathology of TNBS-induced colitis in mice, indicating possible therapeutic potentials for C5a-specific antibody in IBD. The inflammatory bowel diseases (IBDs) encompassing Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders of gastrointestinal tract, characterized by dysfunction of mucosal T cells, abnormal cytokine production, cellular inflammation, and ultimately damage to the intestinal lining. 1 Although the etiology of IBD remains unknown, there is circumstantial evidence to link IBD to the mucosal immune system's failure to attenuate immunity to endogenous antigen. 1 In recent years, several animal IBD models have been developed. 2,3 Although the relationship of many of these models to human disease is imperfect, the hapten-induced model of colonic inflammation in which 2,4,6-trinitrobenzene sulfonic acid (TNBS) is delivered intrarectally to BALB/c mice displays human CD-like features, notably predominantly IL-12-driving Th1 activity of the mucosal CD4 þ T-cell population and transmural mononuclear inflammation. 3 More recently, a pathogenic role of IL-23, the cytokine sharing p40 subunits with IL-12, has been evidenced in the development of CD. 4 Deficiency of IL-23-specific subunits (p19) leads to failure of colitis induction in a T-cell transfer model. This effect is attributed to suppression of IL-17 production and Th17 differentiation in the colons. 5 The factors that initiate intestinal pathology of CD and elicit Th1/Th17 immune reaction, however, are still

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Intestinal Trefoil Factor Induces Decay-Accelerating Factor Expression and Enhances the Protective Activities Against Complement Activation in Intestinal Epithelial Cells

Cited by 56 publications

References 45 publications

Regulation of the Helicobacter pylori Cellular Receptor Decay-accelerating Factor

Regulation of the Helicobacter pylori Cellular Receptor Decay-accelerating Factor

Decay-Accelerating Factor Deficiency Increases Susceptibility to Dextran Sulfate Sodium-Induced Colitis: Role for Complement in Inflammatory Bowel Disease

Blockade of complement activation product C5a activity using specific antibody attenuates intestinal damage in trinitrobenzene sulfonic acid induced model of colitis

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