Title

GM-CSF Induction in Human Lung Fibroblasts by IL-1β, TNF-α, and Macrophage Contact

Document Type

Article

Publication Date

2-1-2003

Description

Fibroblast-derived cytokines may play crucial roles in airway inflammation. In this study, we analyzed expression of the inflammatory cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF), a major eosinophilopoietin, by normal human lung fibroblast (NHLF) cells and its regulation by monokines and macrophage contact. NHLFs were stimulated with interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) and were cocultured with the U937 myelomonocytic cell line. The expression of GM-CSF transcripts was analyzed by reverse transcription-polymerase chain reaction (RT-PCR), and GM-CSF protein was detected by ELISA. Nuclear translocation of nuclear factor-κB (NF-κB), an important transcription factor for inflammatory gene expression, was assessed by electrophoretic mobility shift assay (EMSA). Both IL-1β and TNF-α significantly enhanced the production of GM-CSF by NHLF. Coculturing of peripheral blood mononuclear cells (PBMC) with NHLF induced GM-CSF expression. This phenomenon was also seen on coculturing U937 cells or membranes derived from U937 with NHLF but was inhibited when the two types of cells were separated, suggesting a need for cell-cell contact. U937 membranes, as well as IL-1β and TNF-α, induced nuclear translocation of NF-κB. These data support a prominent role for macrophage-fibroblast interactions in airway inflammation and fibrosis.

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