Progesterone Attenuates Brain Inflammatory Response and Inflammation-Induced Increase in Immature Myeloid Cells in a Mouse Model.
Progesterone Attenuates Brain Inflammatory Response and Inflammation-Induced Increase in Immature Myeloid Cells in a Mouse Model.
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在小鼠模型中，孕酮减弱脑炎症反应和炎症诱导的未成熟髓样细胞增加。
DOI：
10.1007/s10753-020-01390-y
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发表时间：
2021-06
期刊：
影响因子：
5.1
通讯作者：
Beloosesky R
中科院分区：
文献类型：
--
作者：
Gutzeit O;Segal L;Korin B;Iluz R;Khatib N;Dabbah-Assadi F;Ginsberg Y;Fainaru O;Ross MG;Weiner Z;Beloosesky R
孕激素已被证明在怀孕期间调节免疫，孕激素管理可能会减少炎症诱导的早产。我们试图确定妊娠和非妊娠小鼠对LPS诱导的炎症的母体脑免疫反应，以及额外的孕酮补充是否会减弱这种反应。妊娠（P：n = 9）和非妊娠小鼠（NP：n = 9）随机分配至用阴道孕酮/载体（Replens）预处理，从第13天至第16天每天一次。在第15天和第16天，通过腹膜内注射施用LPS/盐水（Replens +盐水n = 3; Replens + LPS n = 3;孕酮+ LPS n = 3）。在第16天处死小鼠，分析母体血清的IL-6水平，分析脑的nNOS、NF-kB、IL-6蛋白水平和未成熟骨髓细胞（IMC）和小胶质细胞活性。LPS显著增加NP和P小鼠的脑nNOS、NF-kB和IL-6，P小鼠的反应显著更大。在NP和P组中，孕酮显著减弱LPS诱导的nNOS和NF-kB的增加，但对血清IL-6无影响。在NP脑中，LPS显着增加IMC人口和孕酮减少IMC表型的水平与对照组相似。在P小鼠中，LPS或LPS +孕酮均未改变脑IMC群体。LPS使NP组和P组小胶质细胞的活性显著增加，孕酮可使其减弱。孕酮减弱NP和P小鼠对LPS的脑炎症反应，尽管它对全身炎症没有影响。在NP小鼠中，孕酮减弱LPS给药后脑IMC的增加。我们的研究结果表明，内源性孕酮在怀孕期间可能会保护大脑免受LPS诱导的炎症。
Progesterone has been shown to regulate immunity during pregnancy, and progesterone administration may reduce inflammation-induced preterm labor. We sought to determine the maternal brain immune response to LPS-induced inflammation in pregnant and non-pregnant mice and whether additional progesterone supplementation attenuates this response. Pregnant (P: n = 9) and non-pregnant mice (NP: n = 9) were randomized to pretreatment with vaginal progesterone/carrier (Replens), daily from days 13 to 16. On days 15 and 16, LPS/saline was administered by intraperitoneal injection (Replens + saline n = 3; Replens + LPS n = 3; progesterone + LPS n = 3). Mice were sacrificed on day 16 and maternal serum analyzed for IL-6 levels and brains analyzed for nNOS, NF-kB, IL-6 protein levels and for immature myeloid cells (IMCs) and microglial activity. LPS significantly increased brain nNOS, NF-kB, and IL-6 in both NP and P mice, with significantly greater responses in P mice. In both NP and P groups, progesterone significantly attenuated LPS-induced increase of nNOS and NF-kB, however with no effect on serum IL-6. In the NP brains, LPS significantly increased IMC population and progesterone reduced the IMC phenotype to levels similar to controls. In P mice, neither LPS nor LPS + progesterone altered the brain IMC population. LPS significantly increased the microglial activity in both NP and P groups, which was attenuated by progesterone. Progesterone attenuates brain inflammatory response to LPS in both NP and P mice although it has no effect on systemic inflammation. In NP mice, progesterone attenuated the increase in brain IMC following LPS administration. Our results suggest that endogenous progesterone during pregnancy may protect the brain from LPS-induced inflammation.
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DOI：
10.3109/14767058.2012.666114
发表时间：
2012-04-01
影响因子：
1.8
作者：
MacIntyre, David A.;Sykes, Lynne;Bennett, Phillip R.
通讯作者：
Bennett, Phillip R.
影响因子：
3.3
作者：
Ginsberg, Yuval;Khatib, Nizar;Beloosesky, Ron
通讯作者：
Beloosesky, Ron
影响因子：
3.4
作者：
Gutzeit, Ola;Segal, Linoy;Fainaru, Ofer
通讯作者：
Fainaru, Ofer
影响因子：
6.2
作者：
El-Etr, Martine;Rame, Marion;Boucher, Celine;Ghoumari, Abdel. M.;Kumar, Narender;Liere, Philippe;Pianos, Antoine;Schumacher, Michael;Sitruk-Ware, Regine
通讯作者：
Sitruk-Ware, Regine
影响因子：
9.8
作者：
Furcron AE;Romero R;Plazyo O;Unkel R;Xu Y;Hassan SS;Chaemsaithong P;Mahajan A;Gomez-Lopez N
通讯作者：
Gomez-Lopez N