A Modified Compound From Paeoniflorin, CP-25, Suppressed Immune Responses and Synovium Inflammation in Collagen-Induced Arthritis Mice.
A Modified Compound From Paeoniflorin, CP-25, Suppressed Immune Responses and Synovium Inflammation in Collagen-Induced Arthritis Mice.
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芍药苷 CP-25 的修饰化合物可抑制胶原诱导的关节炎小鼠的免疫反应和滑膜炎症。
DOI：
10.3389/fphar.2018.00563
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发表时间：
2018
影响因子：
5.6
通讯作者：
Wei W
中科院分区：
文献类型：
--
作者：
Chen J;Wang Y;Wu H;Yan S;Chang Y;Wei W
芍药苷-6 '-O-苯磺酸酯（CP-25）是芍药苷的一种改性产物，是芍药总苷的主要活性成分。本研究评价了CP-25在胶原诱导性关节炎（CIA）小鼠中的抗炎和免疫调节作用以及这些作用的潜在机制。CIA发作后，给予小鼠CP-25（17.5、35或70 mg/kg）或甲氨蝶呤（MTX，2.0 mg/kg）。评价关节炎指数、肿胀关节计数以及关节和脾脏组织病理学。使用流式细胞术测定T和B细胞亚群，同时使用Cell Counting Kit-8评价这些细胞和成纤维细胞样滑膜细胞（FLS）的增殖。采用流式细胞术、免疫组织化学和蛋白质印迹法检测β2-肾上腺素能受体（β2-AR）的表达。用Transwell法检测FLS的迁移和侵袭能力。CP-25（35或70 mg/kg）减轻CIA小鼠的关节炎指数和肿胀关节计数，减轻关节和脾脏组织病理学，抑制过度的T细胞活化，并减弱体液免疫。CP-25增加CIA小鼠T细胞、B细胞、树突状细胞和滑膜上β2-AR的表达。CP-25上调β2-AR激动剂反应并减弱FLS激活;这些作用可能反映了CP-25介导的β2-AR脱敏减少，这是由于下调膜G蛋白偶联受体激酶2表达所致。这些结果表明，CP-25抑制CIA小鼠的免疫应答和滑膜炎症，这种作用与β2-AR脱敏减少和β2-AR信号传导促进有关。
Paeoniflorin-6’-O-benzene sulfonate (CP-25) is a modified paeoniflorin, which is the main bioactive component of total glucosides of peony. This study evaluated the anti-inflammatory and immunoregulatory effects of CP-25 in mice with collagen-induced arthritis (CIA) and the potential mechanisms underlying these effects. After the onset of CIA, mice were given CP-25 (17.5, 35, or 70 mg/kg) or methotrexate (MTX, 2.0 mg/kg). The arthritis index, swollen joint count, and joint and spleen histopathology were evaluated. T and B cell subsets were assayed using flow cytometry, while the proliferation of these cells and fibroblast-like synoviocytes (FLSs) were evaluated using the Cell Counting Kit-8. β2-adrenoceptor (β2-AR) expression was assayed using flow cytometry, immunohistochemistry, and western blotting. FLS migration and invasion were assayed using Transwells. CP-25 (35 or 70 mg/kg) attenuated the arthritis index and swollen joint count, alleviated joint and spleen histopathology, suppressed excessive T cell activation, and attenuated humoral immunity in CIA mice. CP-25 increased β2-AR expression on T cells, B cells, dendritic cells, and the synovium in CIA mice. CP-25 up-regulated the β2-AR agonist response and attenuated FLS activation; these effects may reflect CP-25-mediated reduction of β2-AR desensitization due to down-regulation of membrane G protein-coupled receptor kinase 2 expression. These results suggest that CP-25 suppressed immune responses and synovium inflammation in mice with CIA, effects that were associated with reduced β2-AR desensitization and the promotion of β2-AR signaling.
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影响因子：
4.6
作者：
Dulic S;Vásárhelyi Z;Sava F;Berta L;Szalay B;Toldi G;Kovács L;Balog A
通讯作者：
Balog A
树突状细胞中β2-肾上腺素受体信号传导的减少参与佐剂诱导的关节炎大鼠的炎症反应
影响因子：
4.6
作者：
Wu H;Chen J;Song S;Yuan P;Liu L;Zhang Y;Zhou A;Chang Y;Zhang L;Wei W
通讯作者：
Wei W
DOI：
10.4049/jimmunol.1203045
发表时间：
2013-06-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Rodeghero R;Cao Y;Olalekan SA;Iwakua Y;Glant TT;Finnegan A
通讯作者：
Finnegan A
影响因子：
3.8
作者：
Germolec, DR;Nyska, A;Luster, MI
通讯作者：
Luster, MI
影响因子：
4.4
作者：
Cobelens, PM;Kavelaars, A;Heijnen, CJ
通讯作者：
Heijnen, CJ