Effects of progesterone and estradiol sex hormones on the release of microparticles by RAW 264.7 macrophages stimulated by Poly(I:C).
Effects of progesterone and estradiol sex hormones on the release of microparticles by RAW 264.7 macrophages stimulated by Poly(I:C).
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黄体酮和雌二醇性激素对 Poly(I:C) 刺激的 RAW 264.7 巨噬细胞释放微粒的影响。
DOI：
10.1128/cvi.05110-11
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发表时间：
2011
期刊：
影响因子：
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通讯作者：
Spencer,DianeM
中科院分区：
文献类型：
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作者：
Pisetsky,DavidS;Spencer,DianeM
微粒（MP）是一种小的膜结合囊泡，具有促炎和促血栓形成的特性。这些颗粒可以由巨噬细胞释放，巨噬细胞受Toll样受体（TLR）配体的刺激，在一个依赖于一氧化氮（NO）产生的过程中。由于性激素可以调节巨噬细胞的反应，我们研究了孕酮和雌二醇对巨噬细胞颗粒释放的影响，并与糖皮质激素地塞米松诱导的反应进行了比较。作为颗粒释放的模型系统，RAW 264.7细胞在体外用TLR 3的配体poly（I：C）刺激。通过流式细胞术测量微粒，而通过Griess反应测量NO。这些研究的结果表明，孕酮而不是雌二醇可以阻断用poly（I：C）处理的RAW264.7细胞的颗粒释放;地塞米松也有活性。此外，虽然孕酮和地塞米松在相同的培养条件下抑制NO产生，但两种试剂都不能阻断由NO供体二亚丙基三胺NONOate {（z）-1-[N-（3-氨丙基）-N-（3-氨丙基）氨基]二氮烯-1-鎓-1，2-二醇盐}和（z）-1-[（2-氨乙基）-N-（2-氨乙基）氨基]二氮烯-1-鎓-1，2-二醇盐刺激的颗粒产生。使用RU 486评估激素受体作用的研究表明，虽然该试剂阻断地塞米松对颗粒和NO产生的抑制，但它不影响孕酮的抑制。总之，这些结果表明，孕酮，而不是雌二醇可以抑制颗粒释放刺激的巨噬细胞，并提出了一种机制，可能有助于这种性激素的免疫调节作用。
Microparticles (MPs) are small membrane-bound vesicles that display proinflammatory and prothrombotic properties. These particles can be released by macrophages stimulated by ligands of the Toll-like receptors (TLRs) in a process that depends on nitric oxide (NO) production. Since sex hormones can modulate macrophage responses, we investigated the effects of progesterone and estradiol on macrophage particle releasein vitro, comparing the responses with those induced by the glucocorticoid dexamethasone. As a model system for particle release, RAW 264.7 cells were stimulatedin vitrowith poly(I:C), a ligand of TLR3. Microparticles were measured by flow cytometry, while NO was measured by the Griess reaction. As the results of these studies showed, progesterone but not estradiol can block particle release by RAW264.7 cells treated with poly(I:C); dexamethasone was also active. Furthermore, while progesterone and dexamethasone inhibited NO production under the same culture conditions, neither agent blocked the production of particles stimulated by the NO donors dipropylenetriamine NONOate {(z)-1-[N-(3-aminopropyl)-N-(3-ammoniopropyl)amino] diazen-1-ium-1,2-diolate} and (z)-1-[(2-aminoethyl)-N-(2-ammonioethyl)amino] diazen-1-ium-1,2-diolate. Studies using RU486 to assess the role of hormone receptors indicated that while this agent blocked the inhibition of particle and NO production by dexamethasone, it did not affect the inhibition by progesterone. Together, these results indicate that progesterone but not estradiol can inhibit particle release by stimulated macrophages and suggest a mechanism that may contribute to the immunomodulatory effects of this sex hormone.