Capsaicin, a type of alkaloid and the pungent component of chili peppers, is used as a therapeutic drug against allergic rhinitis and also as an index of bronchial hypersensitivity. Capsaicin receptor (TRPV1) expression has been identified in non-neuronal cells as well as neuronal cells. In our previous study, both TRPV1 protein and its gene expression on nasal epithelial cells were confirmed by immunohistochemistry and RT-PCR, respectively. In order to clarify whether or not TRPV1 acts as a functional receptor, we examined the effects of capsaicin on the production of IL-6 from primary cultured human airway epithelial cells at both protein and mRNA levels. Human nasal epithelial cells (HNECs) and normal human bronchial/tracheal epithelial cells (NHBE cells) were stimulated with increasing concentrations of capsaicin and/or pretreatment with capsazepine (TRPV1 antagonist) at 37 degrees C. The supernatant and total RNA were collected at 0, 4, 12, 24 and 48 h after treatment. IL-6 concentration and the IL-6 mRNA level were evaluated by ELISA and real-time PCR, respectively. Capsaicin (10 nM-10 muM) induced production of IL-6 from HNECs and NHBE cells and this effect was inhibited by pretreatment with capsazepine. Our findings suggest that topical application of capsaicin to the airway induces IL-6 production from respiratory epithelial cells via activation of TRPV1.