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Homocysteine triggers mucosal microvascular activation in inflammatory bowel disease.
Am J Gastroenterol 2005; 100(4):886-95AJ

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.

Authors+Show Affiliations

Department of Internal Medicine, Institute of General Pathology, Catholic University, Rome, Italy. sdanese@hotmail.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

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 -