Interleukin-5 production by human airway epithelial cells

Interleukin (IL)-5 is a pleiotropic cytokine that exhibits biologic activit y on cells of diverse hemopoieitic lineages. IL-5 enhances mediator release from human basophils and plays a pivotal role in the chemoattraction, prol iferation, differentiation, survival, and activation of eosinophils. Th2- a nd Tc2-like T cells, mast cells, basophils, and eosinophils are the known c ellular sources of this cytokine. Using a sensitive and novel reverse trans cription-polymerase chain reaction enzyme-linked immunosorbent assay system , we found that IL-5 messenger RNA (mRNA) was constitutively expressed in b ronchial 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 shedd ing, we hypothesized that epithelial cells might be a source of IL-5 mRNA. We demonstrate here that both transformed human bronchial epithelial cell l ines (A549 and 16HBE14o(-)) and primary human bronchial and nasal epithelia l cells grown in culture constitutively express IL-5 mRNA, which is upregul ated on stimulation with tumor necrosis factor (TNF)-alpha. Culture superna tants derived from A549 cells exposed to TNF-alpha and interferon-gamma dem onstrated detectable levels of IL-5 protein, and immunostaining of bronchia l 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 c ells. This observation provides further evidence for the role of airway epi thelium in regulating airway immune responses, in particular enhancing chem otaxis, activation, and survival of eosinophils, which could play an import ant role in the pathogenesis of bronchial asthma.