Epidermal Growth Factor Receptor Signaling to Erk1/2 and STATs Control the Intensity of the Epithelial Inflammatory Responses to Rhinovirus Infection

摘要: Rhinovirus infection is the most common cause of acute exacerbations inflammatory lung diseases, such as asthma and chronic obstructive pulmonary disease, where it provokes steroid refractory abnormally intense neutrophilic inflammation that can be life threatening. Epidermal growth factor receptor (EGFR) expression correlates with disease severity neutrophil infiltration in these conditions. However, role EGFR signaling rhinovirus unknown. We measured key determinants interleukin (IL)-8 ICAM-1 (RV16 serotype)-infected bronchial epithelial cells, BEAS-2B. RV16 stimulated IL-8 expression, which was further elevated (2-fold) by transient up-regulation levels. Detection viral RNA quantitative real time PCR confirmed enhanced not associated increased replication. ligands (epiregulin, amphiregulin, heparin-binding epidermal factor) were induced infection, inhibition metalloproteases responsible for ligand shedding partially suppressed this response. The inhibitor AG1478, completely blocked to basal levels, did specific Erk1/2 U0126. p38 mitogen-activated protein kinase SB203580 secretion but whereas PI3K wortmannin ineffective both responses. Kinase inactive K721R EGFR, selectively deficient STAT signaling, reversed responses overexpression. In conclusion, rapidly promotes induction utilizes increase These results suggest targeting may provide a selective therapy dampens neutrophil-driven without compromising essential antiviral pathways mediated pathogen recognition receptors TLR3.