Chemokine production by the BEAS-2B human bronchial epithelial cells: Differential regulation of eotaxin, IL-8, and RANTES by T(H)2-and T(H)1-derivedcytokines

Background: Bronchial epithelial cells produce many types of chemokines and may contribute to lung inflammation by recruiting inflammatory cells. The CC chemokine eotaxin is a potent, eosinophil-specific chemoattractant that has been detected in the bronchial epithelium of patients with asthma. Obje ctives: The aim of this study was to investigate the regulatory mechanisms of chemokine production from bronchial epithelium by inflammatory cytokines , especially T(H)2- and T(H)1-derived cytokines, in bronchial asthma. Methods: BEAS-2B human bronchial epithelial cells were cultured with TNF-al pha, IL-4, IL-13, and IFN-gamma alone or in combination, after which supern atants were assayed for eotaxin, IL-8, and RANTES proteins with ELISA. Reve rse transcription-PCR was also performed. Results: TNF-alpha induced production of eotaxin, IL-8, and RANTES in a con centration-dependent manner Both IL-4 and IL-13 synergistically enhanced TN F-alpha-induced eotaxin production, whereas IL-8 plarluction induced by TNF -alpha was significantly down-regulated by the Tea-derived cytokines. IFN-g amma, a T(H)1 cytokine, counteracted the enhancing effects of IL-4 and IL-1 3 on eotaxin production. RANTES production by TNF-alpha was not affected by IL-4 and IL-13 but was markedly enhanced by IFN-gamma. Conclusions:These results suggest that T(H)2 cytokines are involved in pref erential recruitment of eosinophils in bronchial asthma by enhancing eotaxi n and reducing IL-8 production from bronchial epithelial cells and that T(H )1 cytokines counteract the effects of T(H)2 cytokines by reducing eotaxin production.