IL-17-induced cytokine release in human bronchial epithelial cells in vitro:: role of mitogen-activated protein (MAP) kinases
IL-17-induced cytokine release in human bronchial epithelial cells in vitro:: role of mitogen-activated protein (MAP) kinases
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DOI：
10.1038/sj.bjp.0704063
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发表时间：
2001-05-01
影响因子：
7.3
通讯作者：
Lindén, A
中科院分区：
文献类型：
--
作者：
Laan, M;Lötvall, J;Lindén, A
1最近的数据表明，白细胞介素17可能通过诱导中性粒细胞从呼吸道细胞释放细胞因子而参与中性粒细胞炎症。本研究的目的是探讨丝裂原活化蛋白激酶在IL-17诱导的人支气管上皮细胞释放IL-8和IL-6中的作用。两组均给予SB202190(p38MAPK抑制剂)、PD98059(细胞外信号调节激酶途径抑制剂)、Ro-31-7549(蛋白激酶C抑制剂)、LY 294002(磷脂酰肌醇3-激酶抑制剂)或赋形剂治疗。3 SB202190和PD98059呈浓度依赖性地抑制IL-17诱导的人支气管上皮细胞IL-6和IL-8的释放，而不影响细胞的增殖和存活。4 Ro-31-7549和LY294002对IL-17诱导的人支气管上皮细胞IL-6和IL-8的释放没有显著影响。5综上所述，这些数据表明p38和ERK信号通路在IL-17诱导的人支气管上皮细胞释放中性粒细胞动员的细胞因子中起作用。这些机制构成了抑制IL-17介导的呼吸道中性粒细胞增多的潜在药物治疗靶点。
1 Recent data indicate that interleukin (IL)-17 may contribute to neutrophilic airway inflammation by inducing the release of neutrophil-mobilizing cytokines from airway cells. The aim of this study was to evaluate the role of mitogen activated protein kinases in IL-17 induced release of IL-8 and IL-6 in bronchial epithelial cells.2 Transformed human bronchial epithelial cells (16HBE) were stimulated with either IL-17 or vehicle. Both groups were treated either with SB202190 (inhibitor of p38 MAP kinase), PD98059 (inhibitor of extracellular-signal-regulated kinase [ERK] pathway), Ro-31-7549 (protein kinase C [PKC] inhibitor), LY 294002 (a phosphatidylinositol 3-kinase [PI 3-kinase] inhibitor) or vehicle. IL-6 and IL-8 levels were measured in conditioned media by ELISA.3 The IL-17-induced release of IL-6 and IL-8 was concentration-dependently inhibited by SB202190 and by PD98059 in bronchial epithelial cells without affecting cell proliferation or survival.4 Ro-31-7549 and LY294002 had no significant effect on IL-17-induced IL-6 or IL-8 release in bronchial epithelial cells.5 Taken together, these data indicate a role for p38 and ERK kinase pathways in IL-17-induced release of neutrophil-mobilizing cytokines in human bronchial epithelial cells. These mechanisms constitute potential pharmacotherapeutical targets for inhibition of the IL-17-mediated airway neutrophilia.