Expression of glucocorticoid resistance following social stress requires a second signal
Expression of glucocorticoid resistance following social stress requires a second signal
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DOI：
10.1189/jlb.0303090
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发表时间：
2003-10-01
影响因子：
5.5
通讯作者：
Sheridan, JF
中科院分区：
文献类型：
--
作者：
Avitsur, R;Padgett, DA;Sheridan, JF
用革兰氏阴性细菌脂多糖（LPS）刺激社会应激小鼠[社会破坏（SDR）]的脾细胞显示功能性糖皮质激素（GC）抵抗状态。lps刺激的脾细胞对皮质酮的抑制作用不太敏感。本研究表明，脾GC抵抗的表达需要激活信号。结果表明，6个周期的SDR可诱导脾大，增加cd11b阳性单核细胞的数量。SDR还增加了培养的、未受刺激的脾细胞的活力，皮质酮的添加以剂量依赖的方式降低了这些细胞的活力。然而，LPS刺激后，SDR脾细胞对GC的敏感性降低。脂质A是脂多糖分子中与toll样受体（TLR）4结合的一小部分，使用脂质A也获得了类似的结果。此外，不具有功能性TLR4分子的C3H/HeJ小鼠对SDR的反应是脾脏中cd11b阳性单核细胞数量增加，未受刺激的脾细胞活力增加。然而，LPS和脂质A刺激均未导致GC抵抗的表达。综上所述，这些研究结果表明，在SDR的作用下，GC抗性的表达需要通过TLR4的结扎提供第二信号。
Stimulation of splenocytes from socially stressed mice [social disruption (SDR)] with Gram-negative bacterial lipopolysaccharide (LPS) revealed a state of functional glucocorticoid (GC) resistance. LPS-stimulated splenocytes were less sensitive to the inhibitory effects of corticosterone. This study demonstrated that activation signals were required for the expression of splenic GC resistance. The results demonstrated that six cycles of SDR induced splenomegaly and increased the number of CD11b-positive monocytes. SDR also increased the viability of cultured, nonstimulated splenocytes, and addition of corticosterone reduced the viability of these cells in a dose-dependent manner. However, following stimulation with LPS, the sensitivity of SDR splenocytes to GC was reduced. Similar results were obtained using lipid A, a fraction of the LPS molecule that binds to Toll-like receptor (TLR)4. Furthermore, C3H/HeJ mice that do not possess a functional TLR4 molecule responded to SDR with an increased number of CD11b-positive monocytes in the spleen and increased viability of nonstimulated splenocytes. However, neither LPS nor lipid A stimulation resulted in the expression of GC resistance. Together, these findings suggest that the expression of GC resistance in response to SDR requires a second signal that can be provided by ligation of TLR4.