Interleukin-17 stimulates the expression of interleukin-8, growth-related oncogene-alpha, and granulocyte-colony-stimulating factor by human airway epithelial cells.
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.
Jones
Carol E
CE
Novartis Horsham Research Centre, West Sussex, United Kingdom. carol.jones@pharma.novartis.com
Chan
Katie
K
D001483:Base Sequence; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017931:DNA Primers; D003907:Dexamethasone / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics*; D006801:Humans; D020381:Interleukin-17 / Q000502:physiology*; D016209:Interleukin-8 / Q000235:genetics*; D007976:Leupeptins / Q000494:pharmacology; D009857:Oncogenes; D012333:RNA, Messenger / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D017931:DNA Primers; D020381:Interleukin-17; D016209:Interleukin-8; D007976:Leupeptins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D003907:Dexamethasone; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde