Sex and estradiol influence glial pro-inflammatory responses to lipopolysaccharide in rats.
Sex and estradiol influence glial pro-inflammatory responses to lipopolysaccharide in rats.
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DOI：
10.1016/j.psyneuen.2012.02.018
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发表时间：
2012-10
影响因子：
3.7
通讯作者：
Watkins, Linda R.
中科院分区：
文献类型：
--
作者：
Loram, Lisa C.;Sholar, Paige W.;Taylor, Frederick R.;Wiesler, Julie L.;Babb, Jessica A.;Strand, Keith A.;Berkelhammer, Debra;Day, Heidi E. W.;Maier, Steven F.;Watkins, Linda R.
女性患神经炎性疾病的比例高于男性。小胶质细胞是中枢神经系统的主要免疫活性细胞，在神经炎症中起关键作用。我们的目的是确定神经胶质细胞中Toll样受体4介导的促炎反应的固有差异是否可能导致神经炎性疾病的女性患病率偏高。此外，为了确定雌二醇（E2）（主要的女性性类固醇）是否有助于增强促炎反应，在体内和体外均加入雌二醇。小胶质细胞和星形胶质细胞从新生的幼崽和刺激脂多糖（LPS）的存在和不存在的E2。从成年雄性和雌性大鼠中分离海马小胶质细胞，并用LPS离体刺激。雄性新生儿小胶质细胞和星形胶质细胞产生的IL-1β mRNA高于雌性新生儿。然而，当与不同剂量的雌二醇（E2）共孵育时，E2在雄性小胶质细胞中产生抗炎作用，但在雌性小胶质细胞中产生促炎作用。雌激素对雌鼠海马小胶质细胞IL-1β mRNA的表达无明显影响。然而，体内补充E2的雌性动物产生了增强的IL-1β mRNA应答。TLR 4 mRNA在小胶质细胞和星形胶质细胞中均被LPS降低，但不受性别或E2的影响。CD 14 mRNA增加LPS和可能升高更多的女性比男性的小胶质细胞，但不是星形胶质细胞。因此，尽管在分离时小胶质细胞的成熟度影响促炎反应，但在新生儿和成人小胶质细胞中确实存在性二态性差异。
There is a greater prevalence of neuroinflammatory diseases in females than males. Microglia, the major immunocompetent cells of the central nervous system, play a key role in neuroinflammation. We aimed to determine if inherent differences in toll-like receptor 4 mediated pro-inflammatory response in glia could possibly contribute to the skewed female prevalence of neuroinflammatory disorders. In addition, in order to identify if estradiol (E2), the major female sex steroid contributes to a heightened pro-inflammatory response, estradiol was added both in vivo and in vitro. Microglia and astrocytes were isolated from neonatal pups and stimulated with lipopolysaccharide (LPS) in the presence and absence of E2. Hippocampal microglia were isolated from adult male and female rats and stimulated ex vivo with LPS. Male neonatal microglia and astrocytes produced greater IL-1β mRNA than females. However, when co-incubated with varying doses of estradiol (E2), the E2 produced anti-inflammatory effects in the male microglia but a pro-inflammatory effect in female microglia. LPS-induced IL-1β mRNA was attenuated by E2 in female but not male adult hippocampal microglia. However, females supplemented with E2 in vivo produced a potentiated IL-1β mRNA response. TLR4 mRNA was decreased by LPS in both microglia and astrocytes but was not affected by sex or E2. CD14 mRNA was increased by LPS and may be elevated more in females than males in microglia but not astrocytes. Therefore, sexual dimorphic differences do occur in both neonatal and adult microglia though maturity of the microglia at the time of isolation influences the pro-inflammatory response.
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影响因子：
6.2
作者：
Cerciat, M.;Unkila, M.;Arevalo, M. -A.
通讯作者：
Arevalo, M. -A.
影响因子：
4.8
作者：
Brown, Candice M.;Mulcahey, Tara A.;Wise, Phyllis M.
通讯作者：
Wise, Phyllis M.
影响因子：
4.8
作者：
Bruce-Keller, AJ;Keeling, JL;Mattson, MP
通讯作者：
Mattson, MP
影响因子：
4.4
作者：
Achiron, A.;Gurevich, M.
通讯作者：
Gurevich, M.
影响因子：
6.2
作者：
DEGROOT, CJA;HUPPES, W;DIJKSTRA, CD
通讯作者：
DIJKSTRA, CD