Avitsur Ronit, Padgett David A, Dhabhar Firdaus S, Stark Jennifer L, Kramer Kari A, Engler Harald, Sheridan John F
Section of Oral Biology, The Ohio State University, Columbus 43218-2357, USA.
J Leukoc Biol. 2003 Oct;74(4):507-13. doi: 10.1189/jlb.0303090. Epub 2003 Jul 15.
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.
用革兰氏阴性菌脂多糖（LPS）刺激遭受社会应激的小鼠（社会破坏应激，SDR）的脾细胞，发现存在功能性糖皮质激素（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，激活信号是脾GC抵抗表达所必需的。结果表明，六个周期的SDR诱导脾肿大并增加CD11b阳性单核细胞的数量。SDR还增加了培养的未刺激脾细胞的活力，添加皮质酮以剂量依赖性方式降低了这些细胞的活力。然而，在用LPS刺激后，SDR脾细胞对GC的敏感性降低。使用脂多糖分子中与Toll样受体（TLR）4结合的一部分脂多糖（lipid A）也获得了类似结果。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以及未刺激脾细胞的活力增加。然而，LPS和脂多糖（lipid A）刺激均未导致GC抵抗的表达。总之，这些发现表明，对SDR产生的GC抵抗表达需要由TLR4的连接提供的第二个信号。
