Selective estrogen receptor modulators in T cell development and T cell dependent inflammation
Selective estrogen receptor modulators in T cell development and T cell dependent inflammation
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DOI：
10.1016/j.imbio.2015.05.009
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发表时间：
2015-10-01
期刊：
影响因子：
2.8
通讯作者：
Islander, Ulrika
中科院分区：
文献类型：
--
作者：
Bernardi, Angelina I.;Andersson, Annica;Islander, Ulrika
拉索昔芬（las）和巴多昔芬（bza）是第三代选择性雌激素受体调节剂（SERMs），具有最小的雌激素副作用，被批准用于治疗绝经后骨质疏松症。T细胞参与绝经后骨质疏松症的病理学，先前的研究已经确定了17 β-雌二醇（E2）在T细胞发育和功能中的重要作用。E2引起胸腺剧烈萎缩，改变胸腺T细胞群的组成，并抑制T细胞依赖性炎症。相比之下，第二代SERM雷洛昔芬（ral）缺乏这些特性。虽然las和bza是被批准用于治疗绝经后骨质流失的药物，但为了扩大这些化合物的潜在用途，研究它们对其他生物学方面的影响是很重要的。因此，本研究的目的是研究用LAS和BZA治疗是否影响T淋巴细胞生成和T细胞依赖性炎症。将C57 B16小鼠卵巢切除（ovx）并用媒介物、E2、ral、las或bza处理。正如预期的那样，E2降低了胸腺重量，降低了早期T细胞祖细胞的比例，同时增加了胸腺中更成熟的T细胞群。E2还抑制T细胞依赖性迟发型超敏反应（DTH）恶唑酮（OXA）。Ral和las，而不是bza，降低胸腺重量，而没有SERM有任何影响，在胸腺中的T细胞群或炎症的DTH。总之，本研究表明，LAS或BZA治疗不影响T淋巴细胞生成或T细胞依赖性炎症。(C)2015作者由爱思唯尔有限公司出版。
Lasofoxifene (las) and bazedoxifene (bza) are third generation selective estrogen receptor modulators (SERMs) with minimal estrogenic side effects, approved for treatment of postmenopausal osteoporosis. T cells are involved in the pathology of postmenopausal osteoporosis and previous studies have established an important role for 17 beta-estradiol (E2) in T cell development and function. E2 causes a drastic thymic atrophy, alters the composition of thymic T cell populations, and inhibits T cell dependent inflammation. In contrast, the second generation SERM raloxifene (ral) lacks these properties. Although las and bza are drugs approved for treatment of postmenopausal bone loss, it is of importance to study their effects on other biological aspects in order to extend the potential use of these compounds. Therefore, the aim of this study was to investigate if treatment with las and bza affects T lymphopoiesis and T cell dependent inflammation. C57BI6 mice were ovariectomized (ovx) and treated with vehicle, E2, ral, las or bza. As expected, E2 reduced both thymus weight and decreased the proportion of early T cell progenitors while increasing more mature T cell populations in the thymus. E2 also suppressed the T cell dependent delayed-type hypersensitivity (DTH) reaction to oxazolone (OXA). Ral and las, but not bza, decreased thymus weight, while none of the SERMs had any effects on T cell populations in the thymus or on inflammation in DTH. In conclusion, this study shows that treatment with las or bza does not affect T lymphopoiesis or T cell dependent inflammation. (C) 2015 The Authors. Published by Elsevier GmbH.