Heparin Attenuates the Expression of TNF<FONT FACE= HCI Tulip >&#1345;-induced Cerebral Endothelial Cell Adhesion Molecule

Heparin Attenuates the Expression of TNF<FONT FACE= HCI Tulip >&#1345;-induced Cerebral Endothelial Cell Adhesion Molecule

Heparin is a well-known anticoagulant widely used in various clinical settings. Interestingly, recent studies have indicated that heparin also has anti-inflammatory effects on neuroinflammation-related diseases, such as Alzheimer s disease and meningitis. However, the underlying mechanism of its actions remains unclear. In the present study, we examined the anti-inflammatory mechanism of heparin in cultured cerebral endothelial cells (CECs), and found that heparin inhibited the tumor necrosis factor &#1345;(TNF&#1345;)-induced and nuclear factor kappa B (NF-&#1354;B)-dependent expression of adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), which are crucial for inflammatory responses. Heparin selectively interfered with NF-&#1354;B DNA-binding activity in the nucleus, which is stimulated by TNF&#1345;. In addition, non-anticoagulant 2,3-O desulfated heparin (ODS) prevented NF-&#1354;B activation by TNF&#1345;, suggesting that the anti-inflammatory mechanism of heparin action in CECs lies in heparin s ability to inhibit the expression of cell adhesion molecules, as opposed to its anticoagulant actions.