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 - Gasbarrini, Giovanni Battista
AU - Cittadini, Achille
AU - Cittadini, Achille Renato Maria
AU - Gasbarrini, Antonio
PY - 2005
Y1 - 2005
N2 - [Autom. eng. transl.] 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. Patients must assess the levels of plasma and mucosal homocysteine in IBD patients and to assess whether or not they 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 the 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 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 contributing 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
AB - [Autom. eng. transl.] 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. Patients must assess the levels of plasma and mucosal homocysteine in IBD patients and to assess whether or not they 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 the 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 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 contributing 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
KW - homocysteine
KW - homocysteine
UR - http://hdl.handle.net/10807/24039
U2 - 10.1111/j.1572-0241.2005.41469.x
DO - 10.1111/j.1572-0241.2005.41469.x
M3 - Article
SN - 0002-9270
VL - 100
SP - 886
EP - 895
JO - THE AMERICAN JOURNAL OF GASTROENTEROLOGY
JF - THE AMERICAN JOURNAL OF GASTROENTEROLOGY
ER -
