Heparin Attenuates the Expression of TNFalpha-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 alpha(TNFalpha)-induced and nuclear factor kappa B (NF-kappaB)-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-kappaB DNA-binding activity in the nucleus, which is stimulated by TNFalpha. In addition, non-anticoagulant 2,3-O desulfated heparin (ODS) prevented NF-kappaB activation by TNFalpha, 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.
Lee
Jeong Ho
JH
Department of Pharmacology, Brain Research Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
Kim
Chul Hoon
CH
Seo
Gi Ho
GH
Lee
Jinu
J
Kim
Joo Hee
JH
Kim
Dong Goo
DG
Ahn
Young Soo
YS