Silica-induced chemokine expression in alveolar type II cells is mediated by TNF-α
Silica-induced chemokine expression in alveolar type II cells is mediated by TNF-α
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DOI：
10.1152/ajplung.1998.275.6.l1110
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发表时间：
1998-12-01
影响因子：
4.9
通讯作者：
Finkelstein, JN
中科院分区：
文献类型：
--
作者：
Barrett, EG;Johnston, C;Finkelstein, JN
最近的证据表明，接触结晶二氧化硅后，上皮细胞可能通过产生特定的生长因子、趋化因子和细胞因子并对其做出反应，从而导致肺部的炎症反应。然而，上皮细胞对二氧化硅暴露的确切细胞和分子反应仍不清楚。使用小鼠肺泡 II 型细胞系 [小鼠肺上皮 (MLE)-15 细胞系]，我们测量了细胞单独或组合暴露于 4-35 μg/cm(2) 二氧化硅（方英石）、干扰素 (IFN)-γ、肿瘤坏死因子 (TNF)-α 和脂多糖 (LPS) 后各种细胞因子和趋化因子 mRNA 种类的早期变化。暴露 6 小时和 24 小时后，分离总 mRNA，并使用 RNase 保护测定进行测定。单独接触方英石会导致单核细胞趋化蛋白 (MCP)-1、巨噬细胞炎症蛋白 (MIP)-2 增加，并调节正常 T 细胞表达和分泌 (RANTES) mRNA 的激活。单独使用 IFN-γ 治疗可增加 MCP-1 mRNA 水平。单独使用 TNF-α 或 LPS 治疗会导致 MCP-1 和 MIP-2 mRNA 增加。方英石与 TNF-α 的组合导致 MCP-1 和 MIP-2 的额外增加，而方英石与 IFN-γ 或 LPS 则具有协同作用。我们还通过 TNF-α 中和抗体发现，TNF-α 在介导 II 型细胞趋化因子对方英石暴露的反应中发挥着重要作用。结果表明，方英石诱导的肺上皮趋化因子反应部分由 TNF-α 介导，并且可以通过巨噬细胞和淋巴细胞衍生的炎症介质以相加和协同的方式增强。
Recent evidence has suggested that epithelial cells may contribute to the inflammatory response in the lung after exposure to crystalline silica through the production of and response to specific growth factors, chemokines, and cytokines. However, the exact cellular and molecular responses of epithelial cells to silica exposure remains unclear. Using a murine alveolar type II cell line [murine lung epithelial (MLE)-15 cell line], we measured the early changes in various cytokine and chemokine mRNA species after exposure of the cells to 4-35 mu g/cm(2) of silica (cristobalite), interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and lipopolysaccharide (LPS) alone or in combination. Total mRNA was isolated and assayed with an RNase protection assay after 6 and 24 h of exposure. Cristobalite exposure alone led to an increase in monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-2, and regulated on activation normal T cells expressed and secreted (RANTES) mRNAs. Treatment with IFN-gamma alone increased MCP-1 mRNA levels. Treatment with TNF-alpha or LPS alone led to an increase in MCP-1 and MIP-2 mRNA. The combination of cristobalite plus TNF-alpha led to an additive increase in MCP-1 and MIP-2, whereas cristobalite plus IFN-gamma or LPS had a synergistic effect. We also found with a TNF-alpha-neutralizing antibody that TNF-alpha plays a major role in mediating the type II cell chemokine response to cristobalite exposure. The results indicate that the cristobalite-induced chemokine response in the lung epithelium is mediated in part by TNF-alpha and can be enhanced by macrophage- and lymphocyte-derived inflammatory mediators in an additive and synergistic fashion.