Respiratory epithelial cells release interleukin-8 in response to a thermophilic bacteria that causes hypersensitivity pneumonitis.
Hypersensitivity pneumonitis (HP) is a granulomatous inflammatory lung disease that is usually triggered by organic antigens. At early time points after inhalation of antigen, neutrophilic inflammation is prominent in the lungs. Interleukin (IL)-8 is a potent chemoattractant for neutrophils and it is known that alveolar macrophages can release IL-8 after exposure to organic antigens. However, the role of respiratory epithelial cells in the production of IL-8 in HP is unknown. We exposed A549 epithelial cells to the thermophilic bacteria Saccharopolyspora rectivirgula (SR), and measured IL-8 release via enzyme-linked immunosorbent assay (ELISA) and IL-8 messenger RNA (mRNA) induction via Northern analysis. We observed a dose- and time-dependent release of IL-8 in response to SR. The maximal release of IL-8 was measured at 24-48 hours after exposure. There was also an increase in release of 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 of NF-kappa B, a transcription factor that mediates activation of the IL-8 gene. Both corticosteroids and IL-10 blocked the production of IL-8. The release 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.
Gudmundsson
G
G
Division of Pulmonary, Critical Care and Occupational Medicine, University of Iowa College of Medicine, Iowa City 52242, USA.
Hunninghake
G W
GW
D000542:Alveolitis, Extrinsic Allergic / Q000382:microbiology*; D015152:Blotting, Northern; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D012333:RNA, Messenger / Q000378:metabolism; D016930:Saccharopolyspora / Q000502:physiology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D007375:Interleukin-1; D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D016753:Interleukin-10; D003907:Dexamethasone