Intestinal epithelial cells contribute to the enhanced generation of platelet activating factor in ulcerative colitis.

Ferraris, L.; Karmeli, Fanny; Eliakim, Rami; Klein, John S.; Fiocchi, Claudio; Rachmilewitz, Daniel

doi:10.1136/gut.34.5.665

Cited by 55 publications

(32 citation statements)

References 25 publications

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“…These indicated that PAF might be involved in the pathogenesis of Crohn's disease [142] . The elevated level of PAF in colon was likely to be the result of increased production by colonic epithelial cells [143] , lamina propria mononuclear cells [144] and mast cells, and decreased PAF acetylhydrolase (the major PAF degradation enzyme activity) [145] . In patients with ulcerative colitis, colonic production of PAF was increased in comparison with control patients [146] , and the level of PAF in the stool of patients with ulcerative colitis was much higher than that in the stool of healthy volunteers [147] .…”

Section: Involvement Of Pgd2 Ltc4 and Paf In Pathogenesis Of Ibdmentioning

confidence: 99%

Key role of mast cells and their major secretory products in inflammatory bowel disease

He¹

2004

WJG

227

173

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Historically, mast cells were known as a key cell type involved in type I hypersensitivity. Until last two decades, this cell type was recognized to be widely involved in a number of non-allergic diseases including inflammatory bowel disease (IBD). Markedly increased numbers of mast cells were observed in the mucosa of the ileum and colon of patients with IBD, which was accompanied by great changes of the content in mast cells such as dramatically increased expression of TNFα, IL-16 and substance P. The evidence of mast cell degranulation was found in the wall of intestine from patients with IBD with immunohistochemistry technique. The highly elevated histamine and tryptase levels were detected in mucosa of patients with IBD, strongly suggesting that mast cell degranulation is involved in the pathogenesis of IBD. However, little is known of the actions of histamine, tryptase, chymase and carboxypeptidase in IBD. Over the last decade, heparin has been used to treat IBD in clinical practice. The low molecular weight heparin (LMWH) was effective as adjuvant therapy, and the patients showed good clinical and laboratory response with no serious adverse effects. The roles of PGD2, LTC4, PAF and mast cell cytokines in IBD were also discussed. Recently, a series of experiments with dispersed colon mast cells suggested there should be at least two pathways in man for mast cells to amplify their own activationdegranulation signals in an autocrine or paracrine manner. The hypothesis is that mast cell secretogogues induce mast cell degranulation, release histamine, then stimulate the adjacent mast cells or positively feedback to further stimulate its host mast cells through H 1 receptor. Whereas released tryptase acts similarly to histamine, but activates mast cells through its receptor PAR-2. The connections between current anti-IBD therapies or potential therapies for IBD with mast cells were discussed, implicating further that mast cell is a key cell type that is involved in the pathogenesis of IBD. In conclusion, while pathogenesis of IBD remains unclear, the key role of mast cells in this group of diseases demonstrated in the current review implicates strongly that IBD is a mast cell associated disease. Therefore, close attentions should be paid to the role of mast cells in IBD.He SH. Key role of mast cells and their major secretory products in inflammatory bowel disease.

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Section: Involvement Of Pgd2 Ltc4 and Paf In Pathogenesis Of Ibdmentioning

confidence: 99%

Key role of mast cells and their major secretory products in inflammatory bowel disease

He¹

2004

WJG

227

173

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“…These cells present antigens via class II molecule expression (Mayer et al, 1991;Lowes et al, 1992), express adhesion proteins such as intracellular adhesion molecule-i (Kaiserlian et al, 1991) and generate soluble inflammatory mediators e.g. arachidonic acid derivatives (Gustafson & Tagesson, 1990;Dias et al, 1992), platelet activating factor (Ferraris et al, 1993), and cytokines (Spriggs et al, 1988;Hedges et al, 1992;Eckmann et al, 1993;Schuerer-Maly et al, 1994;Gross et al, 1995), all of which contribute to the communication between inflammatory cells and cells of the immune system (Sartor, 1994). Several proinflammatory mediators such as interleukin-1 (IL-1), interleukin-6 (IL-6), leukotrienes, tumour necrosis factor-a (TNF-a), prostaglandins, and complement are increased in actively inflamed colonic tissues from patients with inflammatory bowel disease (Lichtman & Sartor, 1993).…”

Section: Introductionmentioning

confidence: 99%

Interleukin‐8 production by the human colon epithelial cell line HT‐29: modulation by interleukin‐13

Kolios

Robertson

Jordan

et al. 1996

British J Pharmacology

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We have determined which cytokines induce and modulate the production of the chemokine interleukin‐8 (IL‐8) by the human colonic epithelial cell line HT‐29. Growth arrested cell cultures were stimulated with the human recombinant cytokines interleukin‐1α (IL‐1α), tumour necrosis factor‐α (TNF‐α), interferon‐γ (IFN‐γ), interleukin‐13 (IL‐13), interleukin‐10 (IL‐10) or vehicle added alone or in combination. The production of IL‐8 was determined by enzyme‐linked immunosorbent assay (ELISA) and IL‐8 messenger RNA expression by Northern blot analysis. The production of IL‐8 in unstimulated cells was undetectable by both ELISA and Northern blot analysis. HT‐29 cells produced IL‐8 following stimulation with IL‐1α or TNF‐α in a time‐ and a concentration‐dependent manner, while IFN‐γ, IL‐10 and IL‐13 did not induce IL‐8 production by HT‐29 cells. IL‐13 was found to up‐regulate significantly (P < 0.01) the IL‐1α but not the TNF‐α‐induced IL‐8 generation by HT‐29 cells. In contrast, IL‐10 had no effect on either IL‐1α or TNF‐α‐induced IL‐8 production. Experiments using cycloheximide demonstrated that this synergistic effect of IL‐13 and IL‐1α on IL‐8 secretion was not through de novo protein synthesis. Using actinomycin‐D, we demonstrated that the IL‐13 up‐regulation was at the level of transcription rather than messenger RNA stability. These findings suggest that colonic epithelial cells have a functional IL‐13 receptor, which is coupled to an up‐regulation of IL‐1α, but not TNF‐α induced IL‐8 generation.

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“…PAF is produced by intestinal epithelial cells 24 and these cells express PAF-receptors. 36 PAF has been found to have potent chemotactic properties on neutrophils via the production of endogenous leukotriene B4.…”

Section: Cxcl2 C C Lps Ctrol Abmentioning

confidence: 99%

“…21 Other investigators have found that LPS stimulates intestinal epithelial cells to produce TNF 22,23 and PAF. 24 Thus, it is possible that LPS may directly stimulate enterocytes to express CXCL2 via the activation of NFjB, and this effect may be mediated via endogenous production of TNF and PAF.…”

mentioning

confidence: 99%

Lipopolysaccharide induces CXCL2/macrophage inflammatory protein‐2 gene expression in enterocytes via NF‐κB activation: independence from endogenous TNF‐α and platelet‐activating factor

Plaen¹,

Han²,

Liu³

et al. 2006

Immunology

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SummaryCXCL2 (macrophage inflammatory protein-2 (MIP-2)), a critical chemokine for neutrophils, has been shown to be produced in the rat intestine in response to platelet-activating factor (PAF) and to mediate intestinal inflammation and injury. The intestinal epithelium, constantly exposed to bacterial products, is the first line of defence against micro-organisms. It has been reported that enterocytes produce proinflammatory mediators, including tumour necrosis factor (TNF) and PAF, and we showed that lipopolysaccharide (LPS) and TNF activate nuclear factor (NF)-jB in enterocytes. However, it remains elusive whether enterocytes release CXCL2 in response to LPS and TNF via a NF-jB-dependent pathway and whether this involves the endogenous production of TNF and PAF. In this study, we found that TNF and LPS markedly induced CXCL2 gene expression in IEC-6 cells, TNF within 30 min, peaking at 45 min, while LPS more slowly, peaking after 2 hr. TNF-and LPS-induced CXCL2 gene expression and protein release were completely blocked by pyrrolidine dithiocarbamate (PDTC) and helenalin, two potent NF-jB inhibitors. NEMO-binding domain peptide, a specific inhibitor of inhibitor protein jB kinase (IKK) activation, a major upstream kinase mediating NF-jB activation, significantly blocked CXCL2 gene expression and protein release induced by LPS. WEB2170 (PAF antagonist) and anti-TNF antibodies had no effect on LPS-induced CXCL2 expression. In conclusion, CXCL2 gene is expressed in enterocytes in response to both TNF and LPS. LPS-induced CXCL2 expression is dependent on NF-jB activation via the IKK pathway. The effect of LPS is independent of endogenous TNF and PAF.

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Intestinal epithelial cells contribute to the enhanced generation of platelet activating factor in ulcerative colitis.

Cited by 55 publications

References 25 publications

Key role of mast cells and their major secretory products in inflammatory bowel disease

Key role of mast cells and their major secretory products in inflammatory bowel disease

Interleukin‐8 production by the human colon epithelial cell line HT‐29: modulation by interleukin‐13

Lipopolysaccharide induces CXCL2/macrophage inflammatory protein‐2 gene expression in enterocytes via NF‐κB activation: independence from endogenous TNF‐α and platelet‐activating factor

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