Respiratory epithelial cells release interleukin-8 in response to a thermophilic bacteria that causes hypersensitivity pneumonitis

Hypersensitivity pneumonitis (HP) is a granulomatous inflammatory lung dise ase that is usually triggered by organic antigens. At early time points aft er inhalation of antigen, neutrophilic inflammation is prominent in the lun gs. Interleukin (IL)-8 is a potent chemoattractant for neutrophils and it i s known that alveolar macrophages can release IL-8 after exposure to organi c antigens. However, the role of respiratory epithelial cells in the Produc tion of IL-8 in HP is unknown. We exposed A549 epithelial cells to the ther mophilic bacteria Saccharopolyspora rectivirgula (SR), and measured IL-8 re lease via enzyme-linked immunosorbent assay (ELISA) and IL-8 messenger RNA (mRNA) induction via Northern analysis. We observed a dose- and time-depend ent release of IL-8 in response to SR. The maximal release of IL-8 was meas ured at 24-48 hours after exposure. There was also an increase in release o f IL-6 in a time-dependent fashion. SR induced a peak increase in IL-8 mRNA at 12-24 hours. SR also triggered expression of the DNA-binding activity o f NF-kappa B, a transcription factor that mediates activation of the IL-8 g ene. Both corticosteroids and IL-10 blocked the Production of IL-8. The rel ease of IL8 was not mediated through IL-1 beta. These data suggest that SR- induced IL-8 production in airway epithelium may play a role in the initial inflammatory response in HP.