Shikonin inhibited mitogen-activated IL-4 and IL-5 production on EL-4 cells through downregulation of GATA-3 and c-Maf induction
Shikonin inhibited mitogen-activated IL-4 and IL-5 production on EL-4 cells through downregulation of GATA-3 and c-Maf induction
复制标题
DOI：
10.1016/j.lfs.2011.07.002
复制
发表时间：
2011-09-12
期刊：
影响因子：
6.1
通讯作者：
Cheng, Yu-Wen
中科院分区：
文献类型：
--
作者：
Lee, Chen-Chen;Kang, Jaw-Jou;Cheng, Yu-Wen
目的：探讨紫草素对佛波醇肉豆蔻酸酯（PMA）联合环磷酸腺苷（cAMP）诱导的T辅助细胞（T-H）2细胞因子产生的影响及其机制。主要方法：我们使用活化的EL-4小鼠T淋巴瘤细胞，该细胞产生白细胞介素（IL）-4和IL-5，但不产生干扰素（IFN）-γ。作为T(H)2细胞样细胞，并用PMA + cAMP处理它们，研究紫草素对T(H)2细胞因子、转录因子以及相关丝裂原激活蛋白激酶(MAPK)/核因子(NF)-kappa B信号通路的影响。主要发现：数据表明，紫草素通过下调GATA结合抑制PMA + cAMP诱导的IL-4和IL-5的mRNA和蛋白表达Protein-3 (GATA-3) 和 c-肌肉腱膜纤维肉瘤 (Maf) 表达，但 T 细胞 (T-bet) 中不表达 T-box。此外，紫草素还能抑制 kappa B (I kappa B) 激酶 (IKK)-beta 和 I kappa B-alpha 抑制剂 p38 的磷酸化，以及随后由 PMA + cAMP 诱导的 I kappa B-alpha 降解；然而，PMA + cAMP 诱导的细胞外信号相关激酶 (ERK) 磷酸化，导致 c-Jun N 末端激酶 (JNK) 的轻微抑制和磷酸化，似乎不受紫草素处理的影响。 意义：本研究表明，通过抑制 p38、IKK-beta 和 I kappa B-α 磷酸化来下调 GATA-3 和 c-Maf 可能有助于紫草素的抑制作用。紫草素对 EL-4T 细胞中丝裂原诱导的 IL-4 和 IL-5 产生的影响。此外，紫草素是治疗过敏性疾病的潜在药物。 (C) 2011 Elsevier Inc. 保留所有权利。
Aim: To investigate the effects of shikonin on phorbol myristate acetate (PMA) plus cyclic adenosine monophosphate (cAMP)-induced T helper (T-H) 2 cell cytokine production, and the underlying mechanism.Main methods: We used activated EL-4 murine T-lymphoma cells, which produce interleukin (IL)-4 and IL-5, but not interferon (IFN)-gamma. as T(H)2 cell-like cells and treated them with PMA + cAMP to investigate the effects of shikonin on T(H)2 cytokines, transcriptional factors, and the related mitogen-activated protein kinase (MAPK)/nuclear factor (NF)-kappa B signaling pathway.Key findings: The data show that shikonin inhibited the PMA + cAMP-induced mRNA and protein expression of IL-4 and IL-5 via the downregulation of GATA-binding protein-3 (GATA-3) and c-musculoaponeurotic fibrosarcoma (Maf) but not T-box expressed in T cells (T-bet). Moreover, shikonin suppressed the phosphorylation of p38, inhibitor of kappa B (I kappa B) kinase (IKK)-beta and I kappa B-alpha, and the subsequent I kappa B-alpha degradation induced by PMA + cAMP; however, the PMA + cAMP-induced phosphorylation of extracellular signal-related kinase (ERK), which resulted in minor inhibition and phosphorylation of c-Jun N-terminal kinase (JNK), seemed to be unaffected by shikonin treatment.Significance: This study suggests that downregulation of GATA-3 and c-Maf via the suppression of p38, IKK-beta and I kappa B-alpha phosphorylation might contribute to the inhibitory effect of shikonin on mitogen-induced IL-4 and IL-5 production in EL-4T cells. Furthermore, shikonin is a potential drug for treating allergic diseases. (C) 2011 Elsevier Inc. All rights reserved.