Proteases from Aspevgillus fumigatus Induce Interleukin (IL)-6 and IL-8 Production in Airway Epithelial Cell Lines by Transcriptional Mechanisms

• Published in: The Journal of infectious diseases 1999-10, Vol.180 (4), p.1267-1274
• Main Authors: Borger, P., Koëter, G. H., Timmerman, J. A. B., Vellenga, E., Tomee, J. F. C., Kauffman, H. F.
• Format: Article
• Language: English
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/315027

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)-κB 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. Posttran-scriptional 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.