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1 Department of Pulmonology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
2 Department of Dermatology, UMC St. Radboud, Nijmegen, Gelderland, The Netherlands
3 Department of Medical Pharmacology, LACDR, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands
* To whom correspondence should be addressed. E-mail: j.b.vos{at}lumc.nl.
The airway epithelium responds to microbial exposure by altering the expression of a variety of genes to increase innate host defense. In this study we aimed to delineate the early transcriptional response in human primary bronchial epithelial cells exposed for 6 hours to a mixture of IL1
and TNF
or heat-inactivated Pseudomonas aeruginosa. Since the molecular mechanisms of epithelial innate host defense tissues are not fully understood, the open-ended expression profiling technique Serial Analysis of Gene Expression (SAGE) was applied to construct gene expression profiles covering 30.000 genes. A number of 292 genes was found to be differentially expressed. Expression of seven genes was confirmed by quantitative real-time PCR. Among differentially expressed genes, four classes or families were identified: keratins, proteinase inhibitors, S100 calcium-binding proteins and IL1 family members. Marked transcriptional changes were observed for keratins that form a key component of the cytoskeleton in epithelial cells. The expression of the antimicrobial proteinase inhibitors Secretory Leukocyte Proteinase Inhibitor and elafin was elevated after microbial or cytokine exposure. Interestingly, expression of numerous S100 family members was observed and eight members, including S100A8 and S100A9, were among the most differentially expressed genes. Differential expression was also observed for the interleukin-1 family members IL1
, IL1 receptor antagonist, and IL1F9, a newly discovered IL1 family member. Clustering of differentially expressed genes into biological processes revealed that the early inflammatory response in airway epithelial cells to IL1
/TNF
and P. aeruginosa is characterized by expression of genes involved in epithelial barrier formation and host defense.
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