Am. J. Respir. Cell Mol. Biol., Volume 20, Number 5, May, 1999 984-991

Interleukin-5 Production by Human Airway Epithelial Cells

Sundeep Salvi, Amanda Semper, Anders Blomberg, John Holloway, Zeina Jaffar, Alberto Papi, Louis Teran, Ricardo Polosa, Frank Kelly, Thomas Sandström, Stephen Holgate, and Anthony Frew

Department of Medicine, University of Southampton, Southampton, United Kingdom; Department of Allergology and Pulmonology, University Hospital of Northern Sweden, Umeå, Sweden; and Department of Cardiovascular Research, St. Thomas' Hospital, London, United Kingdom

Interleukin (IL)-5 is a pleiotropic cytokine that exhibits biologic activity on cells of diverse hemopoieitic lineages. IL-5 enhances mediator release from human basophils and plays a pivotal role in the chemoattraction, proliferation, differentiation, survival, and activation of eosinophils. Th2- and Tc2-like T cells, mast cells, basophils, and eosinophils are the known cellular sources of this cytokine. Using a sensitive and novel reverse transcription-polymerase chain reaction enzyme-linked immunosorbent assay system, we found that IL-5 messenger RNA (mRNA) was constitutively expressed in bronchial biopsies obtained from healthy individuals, and that the levels of IL-5 mRNA expression decreased 1.5 h after exposure to 0.12 ppm ozone for 2 h. Because the oxidative effects of ozone are confined to the epithelial cell surface and it is known that ozone induces epithelial damage and shedding, we hypothesized that epithelial cells might be a source of IL-5 mRNA. We demonstrate here that both transformed human bronchial epithelial cell lines (A549 and 16HBE14o) and primary human bronchial and nasal epithelial cells grown in culture constitutively express IL-5 mRNA, which is upregulated on stimulation with tumor necrosis factor (TNF)-. Culture supernatants derived from A549 cells exposed to TNF- and interferon- demonstrated detectable levels of IL-5 protein, and immunostaining of bronchial biopsies obtained from healthy human airways revealed the presence of IL-5 protein localized to the bronchial epithelium. To our knowledge, this is the first report demonstrating IL-5 production by human airway epithelial cells. This observation provides further evidence for the role of airway epithelium in regulating airway immune responses, in particular enhancing chemotaxis, activation, and survival of eosinophils, which could play an important role in the pathogenesis of bronchial asthma.

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