IL-13 induces mucin production by stimulating epidermal growth factor receptors and by activating neutrophils

Mucus hypersecretion contributes to the morbidity and mortality in acute as thma. Both T helper 2 (Th2) cytokines and epidermal growth factor receptor (EGFR) signaling have been implicated in allergen-induced goblet cell (GC) metaplasia. Present results show that a cascade of EGFR involving neutrophi ls is implicated in interleukin (IL)-13-induced mucin expression in GC. Tre atment with a selective EGFR tyrosine kinase inhibitor prevented IL-13-indu ced GC metaplasia dose dependently and completely. Instillation of IL-13 al so induced tumor necrosis factor-alpha protein expression, mainly in infilt rating neutrophils. Control airway epithelium contained few leukocytes, but intratracheal instillation of IL-13 resulted in time-dependent leukocyte r ecruitment by IL-13-induced IL-8-like chemoattractant expression in airway epithelium. Pretreatment with an inhibitor of leukocytes in the bone marrow (cyclophosphamide) or with a blocking antibody to IL-8 prevented both IL-1 3-induced leukocyte recruitment and GC metaplasia. These findings indicate that EGFR signaling is involved in IL-13-induced mucin production. They sug gest a potential therapeutic role for inhibitors of the EGFR cascade in the hypersecretion that occurs in acute asthma.