Document Detail


Inflammation pro-resolving potential of 3,4-dihydroxyacetophenone through 15-deoxy-delta12,14-prostaglandin J2 in murine macrophages.
MedLine Citation:
PMID:  17761349     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
3,4-dihydroxyacetophenone (DHAP), an active component isolated from leaves of Tumaodongqing (Ilex Pubescens Hook. Et Arn. Var glaber Chang), is initially used to treat cardiovascular diseases. Previously, we found it had anti-inflammatory effect on macrophages by reducing the production of TNF-alpha in vitro. To further determine whether DHAP could influence inflammatory resolution, 15-deoxy-Delta(12,14)-prostaglandin J(2) (15dPGJ(2)), an arachidonic acid metabolite and also crucial pro-resolving mediator in inflammation, was chosen as the research target. It showed that 10(-5) M DHAP resulted in obvious increase of 15dPGJ(2) in LPS-activated macrophages. Further, inflammation related cytokines and cell apoptosis were also studied. We found DHAP could markedly inhibit LPS-stimulated production of TNF-alpha. However, it could not change the level of IL-10 obviously. At the same time, LPS-triggered apoptosis of macrophage was enhanced by DHAP significantly. After different kinds of cyclooxygenase (COX) inhibitors were administrated, it showed that the effects of DHAP on TNF-alpha and apoptosis were COX-2 dependent. While, inhibition of both COX-1 and COX-2 with indomethacin and administration of 15dPGJ(2) simultaneous reserved the effect of DHAP to inhibit TNF-alpha and enhance apoptosis in LPS-activated macrophages at least partly. The level of COX-2 mRNA and protein were also detected. It was showed that DHAP could increase the expression of COX-2 at both mRNA and protein levels in LPS-activated macrophages. Our results suggest that DHAP could accelerate resolution phase of acute inflammation though enhance the production of 15dPGJ(2), which was also proved to mediate the function of DHAP to inhibit TNF-alpha and enhance apoptosis in vitro. These results are potentially valuable for future use of DHAP.
Authors:
Ping Wu; Li Zhang; Xiaoyan Zhou; Yongsheng Li; Daijuan Zhang; Jinyuan Wan; Duyun Ye
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International immunopharmacology     Volume:  7     ISSN:  1567-5769     ISO Abbreviation:  Int. Immunopharmacol.     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-08-31     Completed Date:  2008-02-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100965259     Medline TA:  Int Immunopharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1450-9     Citation Subset:  IM    
Affiliation:
Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei Province, 430030, China.
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MeSH Terms
Descriptor/Qualifier:
Acetophenones / pharmacology*
Animals
Apoptosis / drug effects
Cell Line
Cyclooxygenase 2 / genetics,  metabolism
Cyclooxygenase 2 Inhibitors / pharmacology
Cytokines / metabolism
Gene Expression Regulation, Enzymologic
Inflammation / drug therapy*
Macrophages / drug effects*,  immunology,  metabolism*
Mice
Prostaglandin D2 / analogs & derivatives*,  metabolism
RNA, Messenger / metabolism
Chemical
Reg. No./Substance:
0/15-deoxy-delta(12,14)-prostaglandin J2; 0/Acetophenones; 0/Cyclooxygenase 2 Inhibitors; 0/Cytokines; 0/RNA, Messenger; 1197-09-7/3,4-dihydroxyacetophenone; 41598-07-6/Prostaglandin D2; EC 1.14.99.-/Ptgs2 protein, mouse; EC 1.14.99.1/Cyclooxygenase 2

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