Disease relevance of VCAM1

• The role of the very late antigen-4 and its counterligand vascular cell adhesion molecule-1 in the pathogenesis of experimental autoimmune neuritis of the Lewis rat [1].
• These data indicate that VCAM-1-mediated adhesion processes are involved in immune-mediated and ischemic diseases of the nervous system but not in T cell-independent macrophage recruitment during Wallerian degeneration [2].
• In addition, VCAM-1 mRNA was detected in the border zone around photochemically induced cerebral infarcts which is the predeliction site of T cell infiltration and expression of immune activation markers during the first week after ischemia [2].
• In the acute phase of experimental autoimmune encephalomyelitis and neuritis VCAM-1 mRNA was expressed not only on the luminal surface of inflamed vessels but also in perivascular cells suggesting a functional role of VCAM-1 in both endothelial adhesion and local restimulation of autoantigen-specific T cells [2].
• Abnormal expression of VCAM-1 has been demonstrated to correlate with the malignant progression of gastric tumors, but the molecular mechanism underlying the VCAM-1-dependent metastasis has been rarely investigated [3].

High impact information on VCAM1

• New transcription of the VCAM1 gene occurred when endothelial cells were treated with TNF [4].
• Fusion plasmids containing the 5' flanking sequence of the VCAM1 gene and the chloramphenicol acetyltransferase reporter gene were used to identify cis-acting sequences that direct the cytokine-induced transcription [4].
• NF-kappa B-mediated activation of VCAM1 gene expression may lead to endothelial expression of a mononuclear leukocyte adhesion molecule associated with initial events in the development of an atherosclerotic lesion [4].
• E(2) decreased LPS-induced VCAM-1 mRNA and protein expression to a greater extent than Dex [5].
• Dex, but not E(2), stabilized VCAM-1 mRNA [5].

Chemical compound and disease context of VCAM1

• We have investigated the functional role of very late antigen-4 [VLA-4 (alpha4/beta1) integrin] and vascular cell adhesion molecule-1 (VCAM-1) in experimental autoimmune neuritis (EAN), an animal model of the Guillain-Barré syndrome, using neutralizing monoclonal antibodies (mAbs) as probes [1].

Biological context of VCAM1

• Upstream of the core promoter, the VCAM1 5' flanking sequence contained a negative regulatory activity [4].
• Transfection of endothelial cells with a functional VCAM-1 promoter construct showed that E(2) inhibited LPS-induced VCAM-1 gene transcription more potently than did Dex [5].
• These experiments demonstrate the critical role of VLA-4 in the pathogenesis of EAN and show that upregulation of VCAM-1 expression contributes, at least in part, to the progression of the disease in the early stages [1].
• Markers of inflammation, especially MHC-II, and cell adhesion molecules, such as VCAM-1, are not expressed on the luminal surface of the barrier under resting conditions [6].
• In summary, different stimuli produced similar expression kinetics of VCAM-1 surface protein but different kinetics of ICAM-1 mRNA expression [7].

Anatomical context of VCAM1

• On immunohistochemical examination, VCAM-1 in sciatic nerve was found to be upregulated at early stages of EAN (days 3-5 after T-cell transfer), whilst no expression was noted in healthy controls [1].
• Blockade of VCAM-1 also significantly ameliorated the disease course and diminished T-cell infiltration in sciatic nerve, but to a lesser degree [1].
• Rottlerin, a protein kinase C (PKC)-delta inhibitor, also blocked beta(2)-integrin adhesion of eosinophils caused by IL-5, whereas beta(1) adhesion to vascular cell adhesion molecule-1 was not affected [8].
• VCAM-1 mRNA was absent from the center of the infarcts as well as axotomized central and peripheral nerves undergoing Wallerian degeneration [2].
• In contrast to MAdCAM-1, phase-dependent protein expression of VCAM-1 was detected in both mammary alveolar tissues and the supramammary lymph nodes, with the highest expression observed in colostral phase cows [9].

Associations of VCAM1 with chemical compounds

• The antiatherogenic effect of estrogen is mediated, in part, by inhibitory effects on endothelial vascular cell adhesion molecule-1 (VCAM-1) expression [5].
• Long-term exposure to high glucose up-regulates VCAM-induced endothelial cell adhesiveness to PBMC [10].
• Cells treated with AGM-1470 had a two- to sevenfold (median fivefold) increase in E-selectin mRNA compared with little or no increase in P-selectin, PECAM-1 and VCAM-1 mRNA [11].

Other interactions of VCAM1

• E. bovis infection upregulated the transcription of genes encoding for P-selectin, E-selectin, vascular cellular adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) [12].
• Moreover, the expression of VCAM-1 and ELAM-1 was lower by 11-14% in both ion dose groups [13].

Analytical, diagnostic and therapeutic context of VCAM1

• Intravenous injection of 500 microg anti-VCAM-1 mAb (5F10) or a corresponding isotype control was given in AT-EAN 4 h before disease induction, and at days 2, 4 and 6 [1].
• In this study we used nonradioactive in situ hybridization for the cellular localization of vascular cell adhesion molecule-1 (VCAM-1) mRNA in immune-mediated, ischemic and degenerative diseases of the rat nervous system [2].
• Western blot analysis and luciferase activity assay showed that anthocyanins inhibited TNF-alpha-induced vascular cell adhesion molecule-1, intracellular adhesion molecule-1, and cyclooxygenase-2 levels, which is through NF-kappaB-dependent pathway [14].
• Semiquantitative Realtime RT-PCR showed upregulated transcription of the E- and P-selectin genes in BUVECs within 1h p.i. and of ICAM-1 and VCAM-1 genes within 2h p.i. Maximum transcript levels were observed at 4-6h p.i.; the 24h p.i. gene transcription had declined to control levels [15].

References