Interleukin-1b augments in vitro alveolar epithelial repair

Geiser, Thomas, Pierre-Henri Jarreau, Kamran Atabai, and Michael A. Matthay. Interleukin-1b augments in vitro alveolar epithelial repair. Am J Physiol Lung Cell Mol Physiol 279: L1184–L1190, 2000.—Biologically active interleukin (IL)-1b 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-1b would enhance wound repair in cultured monolayers from rat alveolar epithelial type II cells. IL-1b (20 ng/ml) increased the rate of in vitro alveolar epithelial repair by 118 6 11% compared with that in serumfree medium control cells (P , 0.01). IL-1b 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-a or inhibition of the EGF receptor by tyrphostin AG-1478 or genistein inhibited IL-1b-induced alveolar epithelial repair, indicating that IL-1b enhances in vitro alveolar epithelial repair by an EGFor transforming growth factor-a-dependent mechanism. Moreover, the mitogen-activated protein kinase pathway is involved in IL-1b-induced alveolar epithelial repair because inhibition of extracellular signal-regulated kinase activation by PD-98059 inhibited IL-1b-induced alveolar epithelial repair. In conclusion, IL-1b augments in vitro alveolar epithelial repair, indicating a possible novel role for IL-1b in the early repair process of the alveolar epithelium in acute lung injury.