Dataset Information
The effects of 17 alpha-estradiol to inhibit inflammation in vitro.
Ontology highlight
ABSTRACT: Background
17 Alpha-estradiol (17 ?-E2) is a natural, non-feminizing stereoisomer of 17 beta-estradiol (17 ?-E2). Whereas much is known about the physiological effects of 17 ?-E2, much less is known about 17 ?-E2. For example, 17 ?-E2 exerts anti-inflammatory effects in neurons and adipocytes through binding and activation of estrogen receptor alpha (ER?); however, if 17 ?-E2 has similar effects on inflammation is currently unknown.Methods
To begin to address this, we analyzed the ability of 17 ?-E2 and 17 ?-E2 to suppress lipopolysaccharide (LPS)-induced inflammation in vitro using embryonic fibroblast cells (MEF) from wild type and total body ER? (ERKO) male and female mice. Additionally, we further probed if there were sex differences with respect to the effects of E2s using primary pre-adipocyte cells from C57BL/6J male and female mice. Also, we probed mechanistically the effects of E2s in fully differentiated 3T3-L1 cells.Results
Both E2s decreased LPS-induced markers of inflammation Tnf-? and Il-6, and increased the anti-inflammatory markers Il-4 and IL-6 receptor (Il-6ra) in MEF cells. To begin to understand the mechanisms by which both E2's mediate their anti-inflammatory effects, we probed the role of ER? using two methods. First, we used MEF cells from ERKO mice and found reductions in ER? diminished the ability of 17 ?-E2 to suppress Tnf-? in female but not in male cells, demonstrating a sexual dimorphism in regard to the role of ER? to mediate 17 ?-E2's effects. Second, we selectively reduced the expression of ER? in 3T3-L1 cells using siRNA and found reductions in ER? diminished the ability of both E2s to suppress Tnf-? and Il-6 expression. Lastly, to determine the mechanisms by which E2s reduce inflammation, we explored the role of NF?B-p65 and found both E2s decreased NF?B-p65 expression.Conclusions
In conclusion, we demonstrate for the first time that 17 ?-E2, as well as 17 ?-E2, suppresses inflammation through their effects on ER? and NF?B-p65.
SUBMITTER: Santos RS
PROVIDER: S-EPMC5586055 | biostudies-literature | 2017 Sep
REPOSITORIES: biostudies-literature
Publications
The effects of 17 alpha-estradiol to inhibit inflammation in vitro.
Biology of sex differences 20170906 1
<h4>Background</h4>17 Alpha-estradiol (17 α-E2) is a natural, non-feminizing stereoisomer of 17 beta-estradiol (17 β-E2). Whereas much is known about the physiological effects of 17 β-E2, much less is known about 17 α-E2. For example, 17 β-E2 exerts anti-inflammatory effects in neurons and adipocytes through binding and activation of estrogen receptor alpha (ERα); however, if 17 α-E2 has similar effects on inflammation is currently unknown.<h4>Methods</h4>To begin to address this, we analyzed th ...[more]
