PMID- 19407978
OWN - NLM
STAT- MEDLINE
DCOM- 20090514
LR  - 20131121
IS  - 0253-6269 (Print)
IS  - 0253-6269 (Linking)
VI  - 32
IP  - 4
DP  - 2009 Apr
TI  - Inhibitory effects of clotrimazole on TNF-alpha-induced adhesion molecule 
      expression and angiogenesis.
PG  - 593-603
LID - 10.1007/s12272-009-1416-6 [doi]
AB  - 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-kappaB activation, as CLT inhibited 
      TNF-alpha-induced ROS generation as well as NF-kappaB nuclear translocation and 
      activation in HT29 cells. Furthermore, the inhibition of TNF-alpha-induced 
      monocyte adhesion was also mimicked by the specific NF-kappaB 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.
FAU - Thapa, Dinesh
AU  - Thapa D
AD  - College of Pharmacy, Yeungnam University, Gyeongsan, 712-749, Korea.
FAU - Lee, Jong Suk
AU  - Lee JS
FAU - Park, Min-A
AU  - Park MA
FAU - Cho, Mi-Yeon
AU  - Cho MY
FAU - Park, Young-Joon
AU  - Park YJ
FAU - Choi, Han Gon
AU  - Choi HG
FAU - Jeong, Tae Cheon
AU  - Jeong TC
FAU - Kim, Jung-Ae
AU  - Kim JA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090429
PL  - Korea (South)
TA  - Arch Pharm Res
JT  - Archives of pharmacal research
JID - 8000036
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (NF-kappa B)
RN  - 0 (Pyrrolidines)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Thiocarbamates)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 25769-03-3 (pyrrolidine dithiocarbamic acid)
RN  - G07GZ97H65 (Clotrimazole)
SB  - IM
MH  - Angiogenesis Inhibitors/*pharmacology
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Cell Adhesion/drug effects
MH  - Chemokine CCL2/metabolism
MH  - Chick Embryo
MH  - Chorioallantoic Membrane/blood supply
MH  - Clotrimazole/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - HT29 Cells
MH  - Humans
MH  - Intercellular Adhesion Molecule-1/*metabolism
MH  - Intestinal Mucosa/*drug effects/immunology
MH  - Monocytes/drug effects/immunology
MH  - NF-kappa B/antagonists & inhibitors/metabolism
MH  - Neovascularization, Physiologic/*drug effects
MH  - Pyrrolidines/pharmacology
MH  - Reactive Oxygen Species/metabolism
MH  - Recombinant Proteins/metabolism
MH  - Thiocarbamates/pharmacology
MH  - Tumor Necrosis Factor-alpha/*metabolism
MH  - U937 Cells
MH  - Vascular Cell Adhesion Molecule-1/*metabolism
EDAT- 2009/05/02 09:00
MHDA- 2009/05/15 09:00
CRDT- 2009/05/02 09:00
PHST- 2009/01/28 00:00 [received]
PHST- 2009/03/19 00:00 [accepted]
PHST- 2009/03/09 00:00 [revised]
PHST- 2009/05/02 09:00 [entrez]
PHST- 2009/05/02 09:00 [pubmed]
PHST- 2009/05/15 09:00 [medline]
AID - 10.1007/s12272-009-1416-6 [doi]
PST - ppublish
SO  - Arch Pharm Res. 2009 Apr;32(4):593-603. doi: 10.1007/s12272-009-1416-6. Epub 2009 
      Apr 29.