PMID- 15784037
OWN - NLM
STAT- MEDLINE
DCOM- 20050429
LR  - 20131121
IS  - 0002-9270 (Print)
IS  - 0002-9270 (Linking)
VI  - 100
IP  - 4
DP  - 2005 Apr
TI  - Homocysteine triggers mucosal microvascular activation in inflammatory bowel 
      disease.
PG  - 886-95
AB  - 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.
FAU - Danese, Silvio
AU  - Danese S
AD  - Department of Internal Medicine, Institute of General Pathology, Catholic 
      University, Rome, Italy. sdanese@hotmail.com
FAU - Sgambato, Alessandro
AU  - Sgambato A
FAU - Papa, Alfredo
AU  - Papa A
FAU - Scaldaferri, Franco
AU  - Scaldaferri F
FAU - Pola, Roberto
AU  - Pola R
FAU - Sans, Miquel
AU  - Sans M
FAU - Lovecchio, Maria
AU  - Lovecchio M
FAU - Gasbarrini, Giovanni
AU  - Gasbarrini G
FAU - Cittadini, Achille
AU  - Cittadini A
FAU - Gasbarrini, Antonio
AU  - Gasbarrini A
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Am J Gastroenterol
JT  - The American journal of gastroenterology
JID - 0421030
RN  - 0 (Chemokine CCL2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 935E97BOY8 (Folic Acid)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Chemokine CCL2/blood
MH  - Colitis, Ulcerative/*physiopathology
MH  - Crohn Disease/*physiopathology
MH  - Endothelium, Vascular/physiopathology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Flow Cytometry
MH  - Folic Acid/blood
MH  - Homocysteine/*physiology
MH  - Humans
MH  - Intercellular Adhesion Molecule-1/blood
MH  - Intestinal Mucosa/*blood supply
MH  - Leukocyte Adherence Inhibition Test
MH  - Male
MH  - Microcirculation/physiopathology
MH  - Middle Aged
MH  - Reference Values
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Vascular Cell Adhesion Molecule-1/blood
EDAT- 2005/03/24 09:00
MHDA- 2005/04/30 09:00
CRDT- 2005/03/24 09:00
PHST- 2005/03/24 09:00 [pubmed]
PHST- 2005/04/30 09:00 [medline]
PHST- 2005/03/24 09:00 [entrez]
AID - AJG41469 [pii]
AID - 10.1111/j.1572-0241.2005.41469.x [doi]
PST - ppublish
SO  - Am J Gastroenterol. 2005 Apr;100(4):886-95. doi: 
      10.1111/j.1572-0241.2005.41469.x.