Stimulation of fibroblast proliferation by growth factors from HCoV-229E-infected human nasal epithelial cells and influenza virus-infected alveolar epithelial cells: Roles of TGF-β1 and FGF-basic.

BACKGROUND

The roles of transforming growth factor (TGF)-β1, fibroblast growth factor basic (FGF-b) and interleukin (IL)-6 released from human coronavirus (HCoV)-229 E-infected human nasal epithelial (HNE) cells and 2009 pandemic influenza virus-infected type II human alveolar epithelial (A549) cells in fibroblast proliferation were studied to elucidate the early mechanisms of airway and lung remodeling initiated by viral infection through epithelial-derived activation of fibroblasts.

METHODS

The number of human fetal lung fibroblasts (MRC-5) cocultured with virus-infected HNE cells or A549 cells, which were cultured using air-interface methods, and the levels of growth factors in supernatants were measured.

RESULTS

The number of MRC-5 cells cocultured with virus-infected HNE cells or A549 cells was greater than that of MRC-5 cells cocultured with uninfected cells. Treatment of MRC-5 cells and cocultured virus-infected HNE or A549 cells with an anti-TGF-β1 antibody and an anti-FGF-b antibody reduced the number of MRC-5 cells. The levels of TGF-β1 and FGF-b in the supernatants of MRC-5 cells cocultured with virus-infected epithelial cells were greater than those in the supernatants of MRC-5 cells cocultured with uninfected cells. Addition of an anti-TGF-β1 antibody reduced FGF-b levels after viral infection. IL-6 levels were increased in HCoV-229 E-infected HNE cells, and treatment with an anti-IL-6 antibody reduced the number of MRC-5 cells cocultured with HCoV-229 E-infected HNE cells. Administration of the p38 MAPK phosphorylation inhibitor SB203580 reduced the number of MRC-5 cells.

CONCLUSIONS

HNE cells and A549 cells may release TGF-β1, FGF-b and IL-6, which increase fibroblast proliferation after viral infection partly via MAPK activation.