Interleukin-17 Stimulates the Expression of Interleukin-8, Growth-Related Oncogene- α, and Granulocyte–Colony-Stimulating Factor by Human Airway Epithelial Cells

Abstract

Interleukin (IL)-17 is a recently discovered cytokine, which is proposed to play a role in neutrophilic airway inflammation via the release of proinflammatory cytokines and chemokines. To evaluate the role of IL-17 in inflammatory protein production from the airway epithelium, we have analyzed the effects of IL-17 on primary human bronchial epithelial cells (HBECs). Using gene arrays, changes in gene expression in response to IL-17 stimulation were investigated and only IL-8, growth-related oncogene (Gro)alpha, and granulocyte colony-stimulating factor (G-CSF) were found to be upregulated. Secretion of IL-8, Groalpha, and G-CSF in response to IL-17 was measured in HBEC cell culture supernatants by enzyme-linked immunosorbent assay. Upregulation of Groalpha, IL-8, and G-CSF was observed to be 8-, 5-, and 8-fold, respectively, after 48 h stimulation with IL-17. When tested at equivalent concentrations, IL-17 was found to be 2- to 3-fold more potent than tumor necrosis factor (TNF)-alpha in stimulating release of Groalpha and G-CSF from HBECs. In addition, IL-17 was found to synergistically enhance TNF-alpha-induced production of IL-8, Groalpha, and G-CSF. It is proposed that IL-17 may play an important role in neutrophil recruitment via stimulating the release of IL-8, Groalpha, and G-CSF from airway epithelial cells.