title: Regulation of human eotaxin generation by Th1-/Th2-derived cytokines.
abstract: BACKGROUND
  Accumulating evidence indicates that eotaxin is the primary mediator of tissue eosinophilia. In the present study, we analyzed the mechanisms of eotaxin generation by Th1-/Th2-derived cytokines in vitro.
  
  
  METHODS
  Human dermal fibroblasts, human umbilical vein endothelial cells and A549 human bronchial epithelial cell line cells were stimulated with TNF-alpha, IL-4, IFN-gamma or TNF-alpha in combination with IL-4 or IFN-gamma and the amount of eotaxin production was analyzed.
  
  
  RESULTS
  Fibroblasts produced nanogram/milliliter quantities of eotaxin. Proinflammatory cytokine TNF-alpha and Th2-type cytokine IL-4 each induced eotaxin production, and combination of them caused a marked synergistic increase in that production. On the other hand, Th1-type cytokine IFN-gamma inhibited eotaxin generation at the protein/mRNA levels.
  
  
  CONCLUSIONS
  The Th2-derived cytokine upregulated while the Th1-derived cytokine inhibited eotaxin production by fibroblasts. In view of the Th1/Th2 paradigm, these results indicate that (1) eotaxin regulates eosinophil accumulation in the Th2-dominant state such as allergic disease, and (2) direct suppression of eotaxin production by IFN-gamma is one of the major mechanisms by which IFN-gamma suppresses eosinophilic inflammation.
authors.affiliation: Department of Allergy and Rheumatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan. misatom-tky@umin.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Miyamasu
authors.forename: Y
authors.initials: Y
authors.lastname: Misaki
authors.forename: M
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Morita
authors.forename: K
authors.initials: K
authors.lastname: Matsushima
authors.forename: T
authors.initials: T
authors.lastname: Nakajima
authors.forename: K
authors.initials: K
authors.lastname: Hirai
mesh_terms: D002460:Cell Line; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines / Q000096:biosynthesis* / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D018417:Th1 Cells / Q000502:physiology*; D018418:Th2 Cells / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C515456:CCL11 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma