Tags

Type your tag names separated by a space and hit enter

Homocysteine triggers mucosal microvascular activation in inflammatory bowel disease.

Abstract

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.

Links

  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Department of Internal Medicine, Institute of General Pathology, Catholic University, Rome, Italy. sdanese@hotmail.com

    , , , , , , , ,

    Source

    MeSH

    Adolescent
    Adult
    Aged
    Chemokine CCL2
    Colitis, Ulcerative
    Crohn Disease
    Endothelium, Vascular
    Enzyme-Linked Immunosorbent Assay
    Female
    Flow Cytometry
    Folic Acid
    Homocysteine
    Humans
    Intercellular Adhesion Molecule-1
    Intestinal Mucosa
    Leukocyte Adherence Inhibition Test
    Male
    Microcirculation
    Middle Aged
    Reference Values
    Tumor Necrosis Factor-alpha
    Vascular Cell Adhesion Molecule-1

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    15784037

    Citation

    Danese, Silvio, et al. "Homocysteine Triggers Mucosal Microvascular Activation in Inflammatory Bowel Disease." The American Journal of Gastroenterology, vol. 100, no. 4, 2005, pp. 886-95.
    Danese S, Sgambato A, Papa A, et al. Homocysteine triggers mucosal microvascular activation in inflammatory bowel disease. Am J Gastroenterol. 2005;100(4):886-95.
    Danese, S., Sgambato, A., Papa, A., Scaldaferri, F., Pola, R., Sans, M., ... Gasbarrini, A. (2005). Homocysteine triggers mucosal microvascular activation in inflammatory bowel disease. The American Journal of Gastroenterology, 100(4), pp. 886-95.
    Danese S, et al. Homocysteine Triggers Mucosal Microvascular Activation in Inflammatory Bowel Disease. Am J Gastroenterol. 2005;100(4):886-95. PubMed PMID: 15784037.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Homocysteine triggers mucosal microvascular activation in inflammatory bowel disease. AU - Danese,Silvio, AU - Sgambato,Alessandro, AU - Papa,Alfredo, AU - Scaldaferri,Franco, AU - Pola,Roberto, AU - Sans,Miquel, AU - Lovecchio,Maria, AU - Gasbarrini,Giovanni, AU - Cittadini,Achille, AU - Gasbarrini,Antonio, PY - 2005/3/24/pubmed PY - 2005/4/30/medline PY - 2005/3/24/entrez SP - 886 EP - 95 JF - The American journal of gastroenterology JO - Am. J. Gastroenterol. VL - 100 IS - 4 N2 - 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. SN - 0002-9270 UR - https://www.unboundmedicine.com/medline/citation/15784037/full_citation L2 - http://Insights.ovid.com/pubmed?pmid=15784037 DB - PRIME DP - Unbound Medicine ER -