Inflammation pro-resolving potential of 3,4-dihydroxyacetophenone through 15-deoxy-delta12,14-prostaglandin J2 in murine macrophages.
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.
Wu
Ping
P
Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei Province, 430030, China.
Zhang
Li
L
Zhou
Xiaoyan
X
Li
Yongsheng
Y
Zhang
Daijuan
D
Wan
Jinyuan
J
Ye
Duyun
D
D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D007249:Inflammation / Q000188:drug therapy*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D000098:Acetophenones; D052246:Cyclooxygenase 2 Inhibitors; D016207:Cytokines; D012333:RNA, Messenger; C032940:3,4-dihydroxyacetophenone; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D015230:Prostaglandin D2