Immunosuppressive Effect of Geniposide on Mitogen-Activated Protein Kinase Signalling Pathway and Their Cross-Talk in Fibroblast-Like Synoviocytes of Adjuvant Arthritis Rats.
Immunosuppressive Effect of Geniposide on Mitogen-Activated Protein Kinase Signalling Pathway and Their Cross-Talk in Fibroblast-Like Synoviocytes of Adjuvant Arthritis Rats.
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京尼平苷对佐剂性关节炎大鼠成纤维样滑膜细胞中丝裂原激活蛋白激酶信号通路及其串扰的免疫抑制作用。
DOI：
10.3390/molecules23010091
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发表时间：
2018-01-02
期刊：
影响因子：
--
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Li F;Dai M;Wu H;Deng R;Fu J;Zhang Z;Dai L;Wang W;Dai X;Zhan X;Wang Y
京尼平苷（GE）是一种来源于栀子果实的环烯醚萜苷类化合物，具有抗炎和免疫调节活性。本研究旨在探讨GE对佐剂性关节炎（AA）大鼠成纤维样滑膜细胞（FLS）中丝裂原活化蛋白激酶（MAPK）信号通路的调控及MAPK信号通路间的相互作用。用弗氏完全佐剂诱导AA。雄性SD大鼠和FLS分别于免疫后第14 ~ 21天体内注射GE（30、60和120 mg/kg）和体外注射GE（25、50和100 μg/mL）。MTT法检测FLS的增殖情况。ELISA法检测IL-4、IL-17、IFN-γ和TGF-β1。Western blot检测MAPK信号通路中的关键蛋白。GE可显著抑制FLS的增殖，沿着IFN-γ和IL-17的降低，IL-4和TGF-β1的升高。此外，GE还能降低AA大鼠FLS中p-JNK、p-ERK 1/2和p-p38的表达。此外，破坏一个MAPK通路抑制其他MAPK通路的激活，这表明MAPK信号之间的串扰。在体内研究中，还观察到GE减轻了AA大鼠滑膜组织的组织病理学变化。总的来说，GE发挥抗炎和免疫调节作用的机制可能与JNK，ERK 1/2和p38的协同作用有关。靶向MAPK信号转导可能是炎症/自身免疫性疾病的一种新的治疗策略。
Geniposide (GE), an iridoid glycoside compound derived from Gardenia jasminoides Ellis fruit, is known to have anti-inflammatory and immunoregulatory activities. The aim of this study was to investigate the protective mechanism of GE in the regulation of the mitogen-activated protein kinase (MAPK) signalling pathway and the cross-talk among the MAPK signalling pathway in fibroblast-like synoviocytes (FLS) of adjuvant arthritis (AA) rats. AA was induced by injecting with Freund’s complete adjuvant. Male SD rats and FLS were subjected to treatment with GE (30, 60 and 120 mg/kg) in vivo from day 14 to 21 after immunization and GE (25, 50 and 100 μg/mL) in vitro, respectively. The proliferation of FLS was assessed by MTT. IL-4, IL-17, IFN-γ, and TGF-β1 were determined by ELISA. Key proteins in the MAPK signalling pathway were detected by Western blot. GE significantly reduced the proliferation of FLS, along with decreased IFN-γ and IL-17 and increased IL-4 and TGF-β1. In addition, GE decreased the expression of p-JNK, p-ERK1/2 and p-p38 in FLS of AA rats. Furthermore, disrupting one MAPK pathway inhibited the activation of other MAPK pathways, suggesting cross-talk among MAPK signalling. In vivo study, it was also observed that GE attenuated histopathologic changes in the synovial tissue of AA rats. Collectively, the mechanisms by which GE exerts anti-inflammatory and immunoregulatory effects may be related to the synergistic effect of JNK, ERK1/2 and p38. Targeting MAPK signalling may be a new therapeutic strategy in inflammatory/autoimmune diseases.
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