IL-17 stimulates inflammatory responses via NF-κB and MAP kinase pathways in human colonic myofibroblasts
IL-17 stimulates inflammatory responses via NF-κB and MAP kinase pathways in human colonic myofibroblasts
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DOI：
10.1152/ajpgi.00494.2001
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发表时间：
2002-06-01
影响因子：
4.5
通讯作者：
Bamba, T
中科院分区：
文献类型：
--
作者：
Hata, K;Andoh, A;Bamba, T
结肠上皮下肌纤维母细胞(SEMF)可能在调节粘膜炎症反应中发挥作用。我们观察了白细胞介素17(IL-17)对结肠半成纤维细胞分泌IL-6和趋化因子[IL-8和单核细胞趋化蛋白(MCP)-1]的影响。用ELISA法和Northern印迹法检测细胞因子的表达。用凝胶迁移率改变分析法(EMSA)检测核因子-kappaB(NF-kappaB)DNA结合活性。免疫印迹法检测丝裂原活化蛋白激酶(MAPK)的活性。IL-17能迅速诱导IL-6、IL-8和MCP-1的分泌。IL-17在刺激后45min内可诱导NF-kappaB活化。阻断核因子-kappaB的激活可显著降低这些反应。丝裂原活化蛋白激酶抑制剂SB-203580、PD-98059和U-0126可显著抑制IL-17诱导的IL-6和趋化因子的分泌。IL-17+IL-1β或IL-17+肿瘤坏死因子-α均可促进细胞因子的分泌，其中IL-17+肿瘤坏死因子-α对IL-6分泌的促进作用明显强于其他两种反应。这依赖于IL-6mRNA稳定性的增强。综上所述，人的自体骨髓基质细胞分泌IL-6、IL-8和MCP-1以响应IL-17。这些反应可能在肠道炎症的发病机制中起重要作用。
Colonic subepithelial myofibroblasts (SEMFs) may play a role in the modulation of mucosal inflammatory responses. We investigated the effects of interleukin (IL)-17 on IL-6 and chemokine [IL-8 and monocyte chemoattractant protein (MCP)-1] secretion in colonic SEMFs. Cytokine expression was determined by ELISA and Northern blotting. Nuclear factor kappa B (NF-kappaB) DNA-binding activity was evaluated by electrophortetic gel mobility shift assay (EMSA). The activation of mitogen-activated protein kinase (MAPK) was assessed by immunoblotting. IL-6, IL-8, and MCP-1 secretions were rapidly induced by IL-17. IL-17 induced NF-kappaB activation within 45 min after stimulation. A blockade of NF-kappaB activation markedly reduced these responses. MAPK inhibitors (SB-203580, PD-98059, and U-0126) significantly reduced the IL-17- induced IL-6 and chemokine secretion. The combination of either IL-17 + IL-1beta or IL-17 + tumor necrosis factor (TNF)-alpha enhanced cytokine secretion; in particular, the effects of IL-17 + TNF-alpha on IL-6 secretion were much stronger than the other responses. This was dependent on the enhancement of IL-6 mRNA stability. In conclusion, human SEMFs secreted IL-6, IL-8, and MCP-1 in response to IL-17. These responses might play an important role in the pathogenesis of gut inflammation.