PMID- 20940016
OWN - NLM
STAT- MEDLINE
DCOM- 20110324
LR  - 20161125
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 650
IP  - 1
DP  - 2011 Jan 10
TI  - Dipyridamole inhibits lipopolysaccharide-induced cyclooxygenase-2 and monocyte 
      chemoattractant protein-1 via heme oxygenase-1-mediated reactive oxygen species 
      reduction in rat mesangial cells.
PG  - 445-50
LID - 10.1016/j.ejphar.2010.09.058 [doi]
AB  - Dipyridamole contributes to its beneficial effects on inflammatory responses in 
      many cell types. The anti-inflammatory mechanisms of dipyridamole on glomerular 
      mesangial cells are mostly uncharacterized. In this study, we monitored the 
      influence of dipyridamole on the expression levels of cyclooxygenase-2 (COX-2) 
      and monocyte chemoattractant protein-1 (MCP-1) in rat mesangial cells stimulated 
      with lipopolysaccharide. Dipyridamole was found to inhibit 
      lipopolysaccharide-induced COX-2 and MCP-1 expression, and reduced 
      lipopolysaccharide-induced reactive oxygen species generation in rat mesangial 
      cells. This inhibitory effect of dipyridamole is independent on cyclic AMP and 
      cyclic GMP increase. Tin protoporphyrin IX (SnPP), a heme oxygenase-1(HO-1) 
      inhibitor, blocked the inhibitory effect of dipyridamole on 
      lipopolysaccharide-induced COX-2 and MCP-1 expression. By applying specific 
      inhibitors in rat mesangial cells, ERK1/2 and p38 MAPK signaling pathways were 
      demonstrated to be involved in the lipopolysaccharide-induced inflammatory 
      responses, and were inhibited by SnPP and N-acetylcysteine treatment. 
      Additionally, dipyridamole was also found to upregulate HO-1 in rat mesangial 
      cells. Therefore, our data suggest that dipyridamole inhibits the expression of 
      COX-2 and MCP-1 in lipopolysaccharide-treated rat mesangial cells via 
      HO-1-mediated reactive oxygen species reduction.
CI  - Copyright (c) 2010 Elsevier B.V. All rights reserved.
FAU - Chen, Yen-Cheng
AU  - Chen YC
AD  - Department of Internal Medicine, Taipei Medical University -Wan Fang Hospital, 
      Taipei, Taiwan.
FAU - Chen, Cheng-Hsien
AU  - Chen CH
FAU - Ko, Wen-Sheng
AU  - Ko WS
FAU - Cheng, Chung-Yi
AU  - Cheng CY
FAU - Sue, Yuh-Mou
AU  - Sue YM
FAU - Chen, Tso-Hsiao
AU  - Chen TH
LA  - eng
PT  - Journal Article
DEP - 20101015
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Reactive Oxygen Species)
RN  - 64ALC7F90C (Dipyridamole)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/pharmacology
MH  - Chemokine CCL2/*metabolism
MH  - Cyclooxygenase 2/*metabolism
MH  - Dipyridamole/*pharmacology
MH  - Gene Expression Regulation, Enzymologic/drug effects
MH  - Heme Oxygenase-1/*metabolism
MH  - Lipopolysaccharides/*antagonists & inhibitors/pharmacology
MH  - Mesangial Cells/*drug effects/enzymology/metabolism
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Phosphorylation/drug effects
MH  - Rats
MH  - Reactive Oxygen Species/*metabolism
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2010/10/14 06:00
MHDA- 2011/03/25 06:00
CRDT- 2010/10/14 06:00
PHST- 2010/01/22 00:00 [received]
PHST- 2010/09/16 00:00 [revised]
PHST- 2010/09/20 00:00 [accepted]
PHST- 2010/10/14 06:00 [entrez]
PHST- 2010/10/14 06:00 [pubmed]
PHST- 2011/03/25 06:00 [medline]
AID - S0014-2999(10)00979-9 [pii]
AID - 10.1016/j.ejphar.2010.09.058 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2011 Jan 10;650(1):445-50. doi: 10.1016/j.ejphar.2010.09.058. 
      Epub 2010 Oct 15.