Proteases from Aspergillus fumigatus induce interleukin (IL)-6 and IL-8 production in airway epithelial cell lines by transcriptional mechanisms.
Proteases secreted by Aspergillus fumigatus induce the production of cytokines by epithelial cells, including interleukin (IL)-6 and IL-8. In the present study, we focused on the mechanism(s) by which A. fumigatus-derived proteases elicit cytokine production in epithelial cells. In the epithelial cell line A549, IL-6 and IL-8 mRNA levels were enhanced by proteases as a result of transcriptional induction of the respective genes. Transcriptional induction of both genes coincided with enhanced DNA binding of nuclear factor (NF)-kappaB and NF-IL6, whereas activator protein-1 was unlikely to be involved. The enhanced transcriptional activity could be inhibited by the addition of chymostatin, showing serine protease dependency. Posttranscriptional mechanisms affecting the stability of IL-6 and IL-8 mRNAs were not involved in protease-induced IL-6 and IL-8 production. These data show that after exposure to A. fumigatus-derived proteases, IL-6 and IL-8 gene expressions are up-regulated as a result of transcriptional mechanisms.
Borger
P
P
Laboratory of Allergology & Pulmonology, Department of Pathology, University Hospital Groningen, 9713 GZ Groningen, The Netherlands. P.Borger@path.azg.nl
Koëter
G H
GH
Timmerman
J A
JA
Vellenga
E
E
Tomee
J F
JF
Kauffman
H F
HF
D001232:Aspergillus fumigatus / Q000201:enzymology*; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism; D010450:Endopeptidases / Q000494:pharmacology*; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology*; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D016209:Interleukin-8 / Q000235:genetics*; D007700:Kinetics; D008175:Lung Neoplasms; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011480:Protease Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects / Q000276:immunology*; D014407:Tumor Cells, Cultured
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D009687:Nuclear Proteins; D011480:Protease Inhibitors; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D010450:Endopeptidases