Inhibitory effects of clotrimazole on TNF-alpha-induced adhesion molecule expression and angiogenesis
- Title
- Inhibitory effects of clotrimazole on TNF-alpha-induced adhesion molecule expression and angiogenesis
- Author
- 최한곤
- Keywords
- Clotrimazole; Monocyte adhesion; ICAM-1; VCAM-1; NF-kappa B; Angiogenesis
- Issue Date
- 2009-04
- Publisher
- PHARMACEUTICAL SOCIETY KOREA
- Citation
- ARCHIVES OF PHARMACAL RESEARCH, v. 32, No. 4, Page. 593-603
- Abstract
- Cell adhesion molecules play a pivotal role in chronic inflammation and pathological angiogenesis. In the present study, we investigated the inhibitory effects of clotrimazole (CLT) on tumor necrosis factor (TNF)-alpha-induced changes in adhesion molecule expression. CLT dose-dependently inhibited monocyte chemoattractant protein-1 (MCP-1), intercellular cell adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) expressions in TNF-alpha-stimulated HT29 colonic epithelial cells. This inhibitory action of CLT correlated with a significant reduction in TNF-alpha-induced adhesion of monocytes to HT29 cells, which was comparable to the inhibitory effects of anti-ICAM-1 and VCAM-1 monoclonal antibodies on monocyte-epithelial adhesion. These inhibitory actions of CLT were, at least in part, attributable to the inhibition of redox sensitive NF-kappa B activation, as CLT inhibited TNF-alpha-induced ROS generation as well as NF-kappa B nuclear translocation and activation in HT29 cells. Furthermore, the inhibition of TNF-alpha-induced monocyte adhesion was also mimicked by the specific NF-kappa B inhibitor, pyrrolidine dithiocarbamate (PDTC). Inflammatory mediators including TNF-alpha have known to promote angiogenesis, which in turn further contributes to inflammatory pathology. Therefore, we additionally evaluated whether CLT modulates TNF-alpha-induced angiogenesis using in vivo chick chorioallantoic membrane (CAM) assay. The CAM assay showed that CLT dose-dependently attenuated TNF-alpha-induced angiogenesis, and the effect was correlated with decreased inflammation of the CAM tissue. In conclusion, our results suggest that CLT can inhibit TNF-alpha-triggered expression of adhesion molecules, ICAM-1 and VCAM-1, and angiogenesis during inflammation.
- URI
- https://link.springer.com/article/10.1007/s12272-009-1416-6https://repository.hanyang.ac.kr/handle/20.500.11754/74956
- ISSN
- 0253-6269
- DOI
- 10.1007/s12272-009-1416-6
- Appears in Collections:
- COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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