Heparin Attenuates the Expression of TNF alpha-induced Cerebral Endothelial Cell Adhesion Molecule.
10.4196/kjpp.2008.12.5.231
- Author:
Jeong Ho LEE
1
;
Chul Hoon KIM
;
Gi Ho SEO
;
Jinu LEE
;
Joo Hee KIM
;
Dong Goo KIM
;
Young Soo AHN
Author Information
1. Department of Pharmacology, Brain Research Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. ahnys@yuhs.ac
- Publication Type:Original Article
- Keywords:
Heparin;
NF-kappa B;
ICAM-1;
VCAM-1;
Cerebral endothelial cells;
Anti-inflammation
- MeSH:
Alzheimer Disease;
Cell Adhesion Molecules;
Endothelial Cells;
Heparin;
Intercellular Adhesion Molecule-1;
Meningitis;
NF-kappa B;
Tumor Necrosis Factor-alpha;
Vascular Cell Adhesion Molecule-1
- From:The Korean Journal of Physiology and Pharmacology
2008;12(5):231-236
- CountryRepublic of Korea
- Language:English
-
Abstract:
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(TNF alpha)-induced and nuclear factor kappa B (NF-kappa 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-kappa B DNA-binding activity in the nucleus, which is stimulated by TNF alpha. In addition, non-anticoagulant 2,3-O desulfated heparin (ODS) prevented NF-kappa B activation by TNF alpha, 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.
