| Homocysteine triggers mucosal microvascular activation in inflammatory bowel disease. | |
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MedLine Citation:
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PMID: 15784037 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVES: Increased homocysteine contributes to the pathophysiology of several chronic inflammatory diseases. Whether homocysteine could participate in mucosal inflammation in inflammatory bowel disease (IBD) has not been explored yet. Our aims were to study the levels of plasma and mucosal homocysteine in IBD patients and to assess whether homocysteine can trigger an inflammatory reaction on human intestinal microvascular endothelial cells (HIMECs). METHODS: Homocysteine was measured in the plasma, mucosal biopsy, and lamina propria mononuclear cell (LPMC) supernatants from normal and IBD subjects. HIMEC were cultured in presence of homocysteine, TNF-alpha, or folic acid, alone or in combination. Expression of vascular cell adhesion molecule 1 (VCAM-1) and intercellular cell adhesion molecule 1 was measured by flow cytometry and monocyte chemoattractant protein-1 (MCP-1) production by ELISA. Phosphorylation of p38 and p42/44 was assessed by immunoblot in HIMEC extracts. T-cell- and monocyte-HIMEC adhesion assays were used to evaluate the impact of homocysteine on leukocyte adhesion to intestinal endothelial cells. RESULTS: Patients with IBD displayed significantly higher homocysteine plasma and mucosal levels than control subjects. IBD-derived LPMC released higher homocysteine than control-derived LPMC. Treatment of HIMEC with homocysteine, and synergistically with the combination of TNF-alpha and homocysteine, triggered HIMEC inflammation, resulting in VCAM-1 up-regulation, MCP-1 production, and p38 phosphorylation. These events lead to an increased capacity of HIMEC to adhere T- and monocyte cells and were blocked by folic acid treatment. CONCLUSIONS: Homocysteine is increased in both the mucosa and plasma of patients with Crohn's disease and ulcerative colitis and contributes to the inflammatory state of the mucosal IBD endothelium. Therefore, homocysteine could play a proinflammatory role in IBD, which can be efficiently targeted by folic acid supplementation. |
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Authors:
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Silvio Danese; Alessandro Sgambato; Alfredo Papa; Franco Scaldaferri; Roberto Pola; Miquel Sans; Maria Lovecchio; Giovanni Gasbarrini; Achille Cittadini; Antonio Gasbarrini |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: The American journal of gastroenterology Volume: 100 ISSN: 0002-9270 ISO Abbreviation: Am. J. Gastroenterol. Publication Date: 2005 Apr |
Date Detail:
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Created Date: 2005-03-23 Completed Date: 2005-04-29 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0421030 Medline TA: Am J Gastroenterol Country: United States |
Other Details:
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Languages: eng Pagination: 886-95 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine, Institute of General Pathology, Catholic University, Rome, Italy. sdanese@hotmail.com |
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Aged Chemokine CCL2 / blood Colitis, Ulcerative / physiopathology* Crohn Disease / physiopathology* Endothelium, Vascular / physiopathology Enzyme-Linked Immunosorbent Assay Female Flow Cytometry Folic Acid / blood Homocysteine / physiology* Humans Intercellular Adhesion Molecule-1 / blood Intestinal Mucosa / blood supply* Leukocyte Adherence Inhibition Test Male Microcirculation / physiopathology Middle Aged Reference Values Tumor Necrosis Factor-alpha / metabolism Vascular Cell Adhesion Molecule-1 / blood |
| Chemical | |
Reg. No./Substance:
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0/Chemokine CCL2; 0/Tumor Necrosis Factor-alpha; 0/Vascular Cell Adhesion Molecule-1; 126547-89-5/Intercellular Adhesion Molecule-1; 454-28-4/Homocysteine; 59-30-3/Folic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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