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 α (TNF α)-induced and nuclear factor kappa B (NF-κB)-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-κ B DNA-binding activity in the nucleus, which is stimulated by TNF α. In addition, non-anticoagulant 2,3-O desulfated heparin (ODS) prevented NF-κB activation by TNF α, 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.
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