Interleukin-1β augments in vitro alveolar epithelial repair

Interleukin-1β augments in vitro alveolar epithelial repair
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DOI:
10.1152/ajplung.2000.279.6.l1184
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发表时间:
2000-12-01
影响因子:
4.9
通讯作者:
Matthay, MA
Matthay, MA
中科院分区:
医学2区
文献类型:
--
作者:
Geiser, T;Jarreau, PH;Matthay, MA

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具有生物活性的白细胞介素 (IL)-1β 存在于从急性肺损伤患者获得的肺水肿液中,并且被认为是非肺上皮伤口修复的重要早期介质。因此,我们测试了以下假设:IL-1β 会增强大鼠 II 型肺泡上皮细胞培养单层细胞的伤口修复。与无血清培养基对照细胞相比,IL-1 beta (20 ng/ml) 使体外肺泡上皮修复率增加 118 +/- 11% (P < 0.01)。 IL-1 诱导伤口边缘的细胞铺展和迁移,但不诱导细胞增殖。表皮生长因子 (EGF) 和转化生长因子-α 的中和抗体或酪氨酸磷酸酶 AG-1478 或染料木黄酮抑制 EGF 受体可抑制 IL-1 β 诱导的肺泡上皮修复,表明 IL-1 β 通过 EGF 或转化生长因子 α 依赖性机制增强体外肺泡上皮修复。此外,丝裂原激活蛋白激酶途径参与 IL-1β 诱导的肺泡上皮修复,因为 PD-98059 抑制细胞外信号调节激酶激活会抑制 IL-1β 诱导的肺泡上皮修复。总之,IL-1β增强体外肺泡上皮修复,表明IL-1β在急性肺损伤肺泡上皮的早期修复过程中可能具有新的作用。
Biologically active interleukin (IL)-1 beta is present in the pulmonary edema fluid obtained from patients with acute lung injury and has been implicated as an important early mediator of nonpulmonary epithelial wound repair. Therefore, we tested the hypothesis that IL-1 beta would enhance wound repair in cultured monolayers from rat alveolar epithelial type II cells. IL-1 beta (20 ng/ml) increased the rate of in vitro alveolar epithelial repair by 118 +/- 11% compared with that in serum-free medium control cells (P < 0.01). IL-1 induced cell spreading and migration at the edge of the wound but not proliferation. Neutralizing antibodies to epidermal growth factor (EGF) and transforming growth factor-alpha or inhibition of the EGF receptor by tyrphostin AG-1478 or genistein inhibited IL-1 beta -induced alveolar epithelial repair, indicating that IL-1 beta enhances in vitro alveolar epithelial repair by an EGF- or transforming growth factor-alpha -dependent mechanism. Moreover, the mitogen-activated protein kinase pathway is involved in IL-1 beta -induced alveolar epithelial repair because inhibition of extracellular signal-regulated kinase activation by PD-98059 inhibited IL-1 beta -induced alveolar epithelial repair. In conclusion, IL-1 beta augments in vitro alveolar epithelial repair, indicating a possible novel role for IL-1 beta in the early repair process of the alveolar epithelium in acute lung injury.