Secretion of MCP‐1, IL‐8 and IL‐6 induced by house dust mite, dermatophagoides pteronissinus in human eosinophilic EOL‐1 cells

Secretion of MCP‐1, IL‐8 and IL‐6 induced by house dust mite, dermatophagoides pteronissinus in human eosinophilic EOL‐1 cells
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屋尘螨、屋尘螨诱导人嗜酸性 EOL-1 细胞分泌 MCP-1、IL-8 和 IL-6

DOI:
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发表时间:
2009
期刊:
影响因子:
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通讯作者:
C. Yun
C. Yun
中科院分区:
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文献类型:
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作者:
Ji;I. Kim;C. Yun

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摘要 屋尘螨(Dermatophagoides pteronissinus)是引发过敏性疾病的重要因素。嗜酸性粒细胞的功能,特别是在细胞因子或趋化因子的产生方面,对于理解炎症性疾病的发病机制至关重要。在本研究中,我们检测了翼龙提取物 (DpE) 是否诱导单核细胞趋化蛋白 1 (MCP-1)/CCL2、IL-8/CXCL8 和 IL-6 的表达,从而介导人嗜酸性细胞系 EoL-1 中免疫细胞的浸润和激活及其信号传导机制。 DpE 在 EoL-1 细胞中以时间和剂量依赖性的方式增加 MCP-1、IL-8 和 IL-6 的 mRNA 和蛋白表达。在使用信号特异性抑制剂的实验中,我们发现 DpE 导致的 MCP-1、IL-8 和 IL-6 表达增加与 Src 家族酪氨酸激酶和蛋白激酶 C δ (PKC δ) 相关。此外,MCP-1和IL-8的表达需要细胞外信号调节激酶(ERK)的激活,而p38丝裂原激活蛋白激酶(MAPK)则参与IL-6的表达。 DpE 诱导 ERK 和 p38 MAPK 磷酸化。 PP2(Src 家族酪氨酸激酶抑制剂)和 Rottlerin(PKC δ 抑制剂)可阻断 ERK 和 p38 MAPK 的激活。 DpE 通过 Src 家族酪氨酸激酶和 PKC δ 诱导 ERK 和 p38 MAPK 的激活,以产生 MCP-1、IL-8 或 IL-6。屋尘螨导致的细胞因子释放增加及其信号转导的特征可能对于理解与嗜酸性粒细胞相关的炎症性疾病的致病机制有价值。
Abstract The house dust mite (Dermatophagoides pteronissinus) is an important factor in triggering allergic diseases. The function of eosinophils, particularly in the production of cytokine or chemokine, is critical in understanding the pathogenesis of inflammatory diseases. In this study, we examined whether D. pteronissinus extract (DpE) induces the expression of monocyte chemotactic protein 1 (MCP‐1)/ CCL2, IL‐8/CXCL8, and IL‐6 that mediate in the infiltration and activation of immune cells and in its signaling mechanism in the human eosinophilic cell line, EoL‐1. DpE increased the mRNA and protein expression of MCP‐1, IL‐8, and IL‐6 in a time‐ and dose‐dependent course in EoL‐1 cells. In our experiments using signal‐specific inhibitors, we found that the increased expression of MCP‐1, IL‐8, and IL‐6 due to DpE is associated with Src family tyrosine kinase and protein kinase C δ (PKC δ). In addition, the activation of extracellular signal‐regulated kinase (ERK) is required for MCP‐1 and IL‐8 expression while p38 mitogen‐activated protein kinase (MAPK) is involved in IL‐6 expression. DpE induced the phosphorylation of ERK and p38 MAPK. PP2, an inhibitor of Src family tyrosine kinase, and rottlerin, an inhibitor of PKC δ, blocked the activation of ERK and p38 MAPK. DpE induces the activation of ERK and p38 MAPK via Src family tyrosine kinase and PKC δ for MCP‐1, IL‐8, or IL‐6 production. Increased cytokine release due to the house dust mite and the characterization of its signal transduction may be valuable in understanding the eosinophil‐related pathogenic mechanism of inflammatory diseases.
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