Cross-talk between Bradykinin and Epidermal Growth Factor in Regulating IL-6 Production in Human Airway Smooth Muscle Cells

Background: Bradykinin (BK), a G-protein-coupled-receptor (GPCR) agonist via the B2receptor induces interleukin (IL)-6 expression in airway smooth muscle(ASM) cells by involving the extracellular signal-regulated kinase 1/2(ERK1/2) signaling pathway. In some cell species, GPCR agonists have beenshown to activate the ERK 1/2 pathway via transactivation of epidermalgrowth factor (EGF) receptor (EGFR). In this study, we tested whether thereis cross-talk between BK and EGF in the regulation of IL-6 gene expressionin ASM cells.Methods: ASM cells were treated with BK, EGF, AG-1478 and genistein. IL-6 productionwas analyzed by enzyme-linked immunosorbent assay (ELISA).Immunoblot study was used for detection of ERK1/2 activation.Transactivation of EGFR phosphorylation was detected by immunoprecipitation.Results: ELISA showed that EGF (10 ng/ml, 18 hr) increased IL-6 secretion (from234