Allergen induced gene expression of airway epithelial cells shows a possible role for TNF-alpha.
BACKGROUND
Epithelium is more than a physical barrier for pathogens and allergens, as it is also capable of producing mediators in response to these environmental factors. Some of these mediators have an immuno-modulatory function, suggesting that epithelium is an active component of the immune response. Here, we fully characterize the expression profile of airway epithelial cells in response to house dust mite (HDM) allergen.


METHODS
H292 cells were exposed to HDM extract for 24 h, RNA and supernatant was used for microarray analysis and multiplex enzyme-linked immunosorbent assay (ELISA) respectively.


RESULTS
A total of 38,500 genes, 813 were differentially expressed by more than twofold and 116 even more than fivefold. Interestingly, among the most up-regulated genes, a large number are involved in cell-to-cell communication. These include chemokines (CCL-8 and -20, CXCL-1, -2 and -3), cytokines (IL-1alpha, -6 and -11), anti-inflammatory factors [PTX-3, interleukin (IL)-13Ralpha, tumour necrosis factor (TNF)-alphaIP3], and factors that are involved in repair of the mucosal tissue (LOXL-2, NID-2, HBEGF, MUC-5AC and MUC-5B). Pathway analysis showed that a number of these genes are transcriptionally regulated by TNF-alpha, which we could detect by quantitative polymerase chain reaction at earlier time points after HDM exposure. In addition, we could detect increased protein levels for TNF-alpha, IL-6, IL8, granulocyte-macrophage colony-stimulating factor, granulocyte colony stimulating factor and interferon (IFN)-gamma using ELISA.


CONCLUSIONS
Our data show that a broad range of mediators produced upon allergen exposure by these mediators' epithelial cells can participate in the immune response via recruitment and activation of cells of the immune system.
Vroling
A B
AB
Department of Otorhinolanyngology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Duinsbergen
D
D
Fokkens
W J
WJ
van Drunen
C M
CM
D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism*; D015870:Gene Expression; D053263:Gene Regulatory Networks; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation
D039741:Antigens, Dermatophagoides; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha