title: Chemokine production by the BEAS-2B human bronchial epithelial cells: differential regulation of eotaxin, IL-8, and RANTES by TH2- and TH1-derived cytokines.
abstract: 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.
  
  
  OBJECTIVE
  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-alpha, IL-4, IL-13, and IFN-gamma alone or in combination, after which supernatants were assayed for eotaxin, IL-8, and RANTES proteins with ELISA. Reverse transcription-PCR was also performed.
  
  
  RESULTS
  TNF-alpha induced production of eotaxin, IL-8, and RANTES in a concentration-dependent manner. Both IL-4 and IL-13 synergistically enhanced TNF-alpha-induced eotaxin production, whereas IL-8 production induced by TNF-alpha was significantly down-regulated by the T(H)2-derived cytokines. IFN-gamma, a T(H)1 cytokine, counteracted the enhancing effects of IL-4 and IL-13 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 preferential recruitment of eosinophils in bronchial asthma by enhancing eotaxin 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.
authors.affiliation: Department of Pediatrics, Mie National Hospital, Tsu, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Fujisawa
authors.forename: Y
authors.initials: Y
authors.lastname: Kato
authors.forename: J
authors.initials: J
authors.lastname: Atsuta
authors.forename: A
authors.initials: A
authors.lastname: Terada
authors.forename: K
authors.initials: K
authors.lastname: Iguchi
authors.forename: H
authors.initials: H
authors.lastname: Kamiya
authors.forename: H
authors.initials: H
authors.lastname: Yamada
authors.forename: T
authors.initials: T
authors.lastname: Nakajima
authors.forename: M
authors.initials: M
authors.lastname: Miyamasu
authors.forename: K
authors.initials: K
authors.lastname: Hirai
mesh_terms: D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002461:Cell Line, Transformed; D054413:Chemokine CCL11; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D018925:Chemokines / Q000096:biosynthesis*; D019742:Chemokines, CC; D016207:Cytokines / Q000378:metabolism / Q000502:physiology; D004357:Drug Synergism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D012333:RNA, Messenger / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C515456:CCL11 protein, human; D054413:Chemokine CCL11; D018946:Chemokine CCL5; D018925:Chemokines; D019742:Chemokines, CC; D016207:Cytokines; D007377:Interleukin-3; D016209:Interleukin-8; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma