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Intestinal Fibroblasts (intestinal + fibroblast)

Distribution by Scientific Domains
Medical Sciences100%

Selected Abstracts

The role of MAPK in governing lymphocyte adhesion to and migration across the microvasculature in inflammatory bowel disease

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2009
Franco Scaldaferri
Abstract Lymphocyte recruitment is a key pathogenic event in inflammatory bowel disease (IBD). Adhesion of T cells to human intestinal microvascular endothelial cells (HIMEC) is mediated by ICAM-1, VCAM-1 and fractalkine (FKN), but the signaling molecules that orchestrate this process have yet to be identified. Because MAPK play an important role in the response of many cell types to pro-inflammatory stimuli, we assessed the functional role of p38 MAPK, p42/44 MAPK and JNK in the regulation of lymphocyte adhesion to and chemotaxis across the microvasculature in IBD. We found that the MAPK were phosphorylated in the bowel microvasculature and human intestinal fibroblasts of patients with IBD but not of healthy individuals. Stimulation of HIMEC with TNF- , triggered phosphorylation of the MAPK, and up-regulation of VCAM-1, FKN and ICAM-1. Blockade of p38 decreased the expression of all MAPK by 50% (p<0.01), whereas inhibition of p42/44 decreased the expression of ICAM-1 and FKN by 50% (p<0.01). Treatment of human intestinal fibroblasts with TNF- , elicited production of IL-8 and MCP-1, which was reduced (p<0.05) by blockade of p38 and p42/44. Finally, blockade of p38 and p42/44 reduced lymphocyte adhesion to (p<0.05) and transmigration across (p<0.05) HIMEC monolayers. These findings suggest a critical role for MAPK in governing lymphocyte influx into the gut in IBD patients, and their blockade may offer a molecular target for blockade of leukocyte recruitment to the intestine. [source]

Authors' reply: Bacterial lipopolysaccharide promotes profibrotic activation of intestinal fibroblasts (Br J Surg 2010; 97: 1126,1134)

BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 11 2010
J. P. Burke
No abstract is available for this article. [source]

Bacterial lipopolysaccharide promotes profibrotic activation of intestinal fibroblasts,

BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 7 2010
J. P. Burke
Background: Fibroblasts play a critical role in intestinal wound healing. Lipopolysaccharide (LPS) is a cell wall component of commensal gut bacteria. The effects of LPS on intestinal fibroblast activation were characterized. Methods: Expression of the LPS receptor, toll-like receptor (TLR) 4, was assessed in cultured primary human intestinal fibroblasts using flow cytometry and confocal microscopy. Fibroblasts were treated with LPS and/or transforming growth factor (TGF) ,1. Nuclear factor ,B (NF,B) pathway activation was assessed by inhibitory ,B, (I,B,) degradation and NF,B promoter activity. Fibroblast contractility was measured using a fibroblast-populated collagen lattice. Smad-7, a negative regulator of TGF-,1 signalling, and connective tissue growth factor (CTGF) expression were assessed using reverse transcriptase,polymerase chain reaction and western blot. The NF,B pathway was inhibited by I,B, transfection. Results: TLR-4 was present on the surface of intestinal fibroblasts. LPS treatment of fibroblasts induced I,B, degradation, enhanced NF,B promoter activity and increased collagen contraction. Pretreatment with LPS (before TGF-,1) significantly increased CTGF production relative to treatment with TGF-,1 alone. LPS reduced whereas TGF-,1 increased smad-7 expression. Transfection with an I,B, plasmid enhanced basal smad-7 expression. Conclusion: Intestinal fibroblasts express TLR-4 and respond to LPS by activating NF,B and inducing collagen contraction. LPS acts in concert with TGF-,1 to induce CTGF. LPS reduces the expression of the TGF-,1 inhibitor, smad-7. Copyright © 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source]

Eosinophil granule-derived major basic protein induces IL-8 expression in human intestinal myofibroblasts

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2000
G. T. Furuta
Eosinophil infiltration occurs in a variety of allergic and inflammatory diseases. The release of preformed mediators from eosinophils may contribute to inflammatory responses. We investigated the ability of eosinophil-derived major basic protein and eosinophil-derived neurotoxin to stimulate production of IL-8 from intestinal myofibroblasts. Intestinal myofibroblasts (18-Co cells) were incubated with major basic protein, eosinophil-derived neurotoxin, or a synthetic analogue of major basic protein, poly- l -arginine. Immunoreactive IL-8 was measured by ELISA and IL-8 mRNA levels were analysed by Northern blot or reverse transcription-polymerase chain assay. Major basic protein induced IL-8 mRNA production and release of significant levels of IL-8 immunoreactive protein. By contrast, eosinophil-derived neurotoxin stimulated little IL-8 release. The induction of IL-8 mRNA by poly- l -arginine was significantly inhibited by actinomycin D. These findings demonstrate a novel interaction between eosinophils and intestinal fibroblasts that may be involved in the pathogenesis of diseases associated with tissue eosinophilia. [source]