Interleukin-13 induces dramatically different transcriptional programs in three human airway cell types

Interleukin (IL)-13, a cytokine released by T lymphocytes during immediate hypersensitivity responses, is a central mediator of asthma. Because IL-13 induces phenotypic features of asthma in mice deficient in T and B lymphocy tes, it is likely that this cytokine contributes to the development of asth ma by acting directly on resident airway cells. To analyze the global effec ts of IL-13 on gene expression in airway cells that could contribute to the phenotypic features of asthma, we used Genechip HuGene FL arrays (Affymetr ix, Santa Clara, CA) that contain probes for approximately 6,500 human gene s. Despite activating a common signaling pathway, IL-13 induced dramaticall y different patterns of gene expression in primary cultures of airway epith elial cells, airway smooth muscle cells, and lung fibroblasts, with little overlap among cell types. The most prominent effects of IL-13 were on airwa y smooth muscle, but several genes induced in airway epithelial cells and f ibroblasts are also candidates that may contribute to phenotypic features o f asthma. These results suggest that the in vivo response to IL-13 in the a irways likely results from a combination of distinct effects on each of sev eral resident airway cell types.