Regulation of human eotaxin generation by Th1-/Th2-derived cytokines.
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.
Miyamasu
M
M
Department of Allergy and Rheumatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan. misatom-tky@umin.ac.jp
Misaki
Y
Y
Yamaguchi
M
M
Yamamoto
K
K
Morita
Y
Y
Matsushima
K
K
Nakajima
T
T
Hirai
K
K
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
C515456:CCL11 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma