PMID- 16543969
OWN - NLM
STAT- MEDLINE
DCOM- 20060427
LR  - 20181201
IS  - 0340-6245 (Print)
IS  - 0340-6245 (Linking)
VI  - 95
IP  - 1
DP  - 2006 Jan
TI  - The estrogen metabolite 17beta-dihydroequilenin counteracts interleukin-1alpha 
      induced expression of inflammatory mediators in human endothelial cells in vitro 
      via NF-kappaB pathway.
PG  - 107-16
AB  - In most studies showing cardio- and vasculoprotective effects of estrogens, 
      17beta-estradiol was used and little information on possible effects of different 
      estrogen metabolites is yet available. We investigated whether particular 
      estrogen metabolites are effective in counteracting inflammatory activation of 
      human endothelium. Human endothelial cells were incubated with 
      17alpha-dihydroequilenin, 17beta-dihydroequilenin, delta-8,9-dehydroestrone, 
      estrone and 17beta-estradiol and stimulated with interleukin (IL)-1alpha. The 
      expression of IL-6, IL-8 and monocyte chemoattractant protein-1 (MCP-1) was 
      determined. 17beta-dihydroequilenin and 17beta-estradiol at a concentration of 1 
      microM reduced IL-1alpha-induced up regulation of IL-6, IL-8 and MCP-1 close to 
      control levels. When both compounds were used in combination an additive effect 
      was observed. 17alpha-dihydroequilenin and delta-8,9-dehydroestrone showed a 
      similar anti-inflammatory effect only when used at 10 microM whereas estrone had 
      no effect. The effect of 17beta-dihydroequilenin on IL-1alpha-induced production 
      of IL-6, IL-8 and MCP-1 was reversed by the estrogen receptor antagonist ICI 
      182,780. 17beta-dihydroequilenin also inhibited IL-1alpha-induced translocation 
      of p50 and p65 to the nucleus of the cells. We have identified the estrogen 
      metabolite 17beta-dihydroequilenin, as an inhibitor of inflammatory activation of 
      human endothelial cells. Characterization of specific estrogens--as shown in our 
      study--could provide the basis for tailored therapies, which might be able to 
      achieve vasoprotection without adverse side effects.
FAU - Demyanets, Svitlana
AU  - Demyanets S
AD  - Department of Internal Medicine II, Medical University Vienna, Waehringer Guertel 
      18-20, A-1090 Vienna, Austria.
FAU - Pfaffenberger, Stefan
AU  - Pfaffenberger S
FAU - Kaun, Christoph
AU  - Kaun C
FAU - Rega, Gersina
AU  - Rega G
FAU - Speidl, Walter S
AU  - Speidl WS
FAU - Kastl, Stefan P
AU  - Kastl SP
FAU - Weiss, Thomas W
AU  - Weiss TW
FAU - Hohensinner, Philipp J
AU  - Hohensinner PJ
FAU - Dietrich, Wolf
AU  - Dietrich W
FAU - Tschugguel, Walter
AU  - Tschugguel W
FAU - Bochkov, Valery N
AU  - Bochkov VN
FAU - Awad, Ezzat M
AU  - Awad EM
FAU - Maurer, Gerald
AU  - Maurer G
FAU - Huber, Kurt
AU  - Huber K
FAU - Wojta, Johann
AU  - Wojta J
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - Germany
TA  - Thromb Haemost
JT  - Thrombosis and haemostasis
JID - 7608063
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Estrogen Antagonists)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Estrogen Receptor beta)
RN  - 0 (Estrogens)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-6)
RN  - 0 (Interleukin-8)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 08O86EX0J4 (Equilin)
RN  - 22X328QOC4 (Fulvestrant)
RN  - 4TI98Z838E (Estradiol)
RN  - 651-55-8 (dihydroequilin)
SB  - IM
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Base Sequence
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Endothelial Cells/*drug effects/metabolism
MH  - Equilin/*analogs & derivatives/pharmacology
MH  - Estradiol/analogs & derivatives/pharmacology
MH  - Estrogen Antagonists/pharmacology
MH  - Estrogen Receptor alpha/drug effects/genetics/metabolism
MH  - Estrogen Receptor beta/drug effects/genetics/metabolism
MH  - Estrogens/metabolism
MH  - Fulvestrant
MH  - Humans
MH  - Interleukin-1/*pharmacology
MH  - Interleukin-6/genetics/metabolism
MH  - Interleukin-8/genetics/metabolism
MH  - Molecular Sequence Data
MH  - NF-kappa B/metabolism
MH  - RNA, Messenger/metabolism
EDAT- 2006/03/18 09:00
MHDA- 2006/04/28 09:00
CRDT- 2006/03/18 09:00
PHST- 2006/03/18 09:00 [pubmed]
PHST- 2006/04/28 09:00 [medline]
PHST- 2006/03/18 09:00 [entrez]
AID - 06010107 [pii]
PST - ppublish
SO  - Thromb Haemost. 2006 Jan;95(1):107-16.