The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Heparin Attenuates the Expression of TNF $\alpha$-induced Cerebral Endothelial Cell Adhesion Molecule

  • Lee, Jeong-Ho (Department of Pharmacology, Brain Research Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine) ;
  • Kim, Chul-Hoon (Department of Pharmacology, Brain Research Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine) ;
  • Seo, Gi-Ho (Department of Pharmacology, Brain Research Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine) ;
  • Lee, Jin-U (Pochun CHA University College of Medicine) ;
  • Kim, Joo-Hee (Department of Pharmacology, Brain Research Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine) ;
  • Kim, Dong-Goo (Department of Pharmacology, Brain Research Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine) ;
  • Ahn, Young-Soo (Department of Pharmacology, Brain Research Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine)
  • Published : 2008.10.31
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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.

Keywords

References

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