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 lymphocytes, it is likely that this cytokine contributes to the development of asthma by acting directly on resident airway cells. To analyze the global effects of IL-13 on gene expression in airway cells that could contribute to the phenotypic features of asthma, we used Genechip HuGene FL arrays (Affymetrix, Santa Clara, CA) that contain probes for approximately 6,500 human genes. Despite activating a common signaling pathway, IL-13 induced dramatically different patterns of gene expression in primary cultures of airway epithelial cells, airway smooth muscle cells, and lung fibroblasts, with little overlap among cell types. The most prominent effects of IL-13 were on airway smooth muscle, but several genes induced in airway epithelial cells and fibroblasts are also candidates that may contribute to phenotypic features of asthma. These results suggest that the in vivo response to IL-13 in the airways likely results from a combination of distinct effects on each of several resident airway cell types.
Lee
J H
JH
Lung Biology Center, Cardiovascular Research Institute, University of California-San Francisco, San Francisco, CA 94143, USA.
Kaminski
N
N
Dolganov
G
G
Grunig
G
G
Koth
L
L
Solomon
C
C
Erle
D J
DJ
Sheppard
D
D
D002478:Cells, Cultured; D010450:Endopeptidases / Q000187:drug effects / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000187:drug effects / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects / Q000235:genetics; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D011480:Protease Inhibitors; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D012137:Respiratory System / Q000166:cytology* / Q000187:drug effects; D050800:STAT6 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000187:drug effects / Q000235:genetics; D014158:Transcription, Genetic
D016326:Extracellular Matrix Proteins; D018793:Interleukin-13; D007473:Ion Channels; D011480:Protease Inhibitors; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators; D010450:Endopeptidases