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. CONCLUSION: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

Miyamasu M,Misaki Y,Yamaguchi M,Yamamoto K,Morita Y,Matsushima K,Nakajima T,Hirai K

doi

10.1159/000053634

keywords:

subject

Has Abstract

pub_date

2000-05-01 00:00:00

pages

54-8

eissn

1018-2438

issn

1423-0097

pii

53634

journal_volume

122 Suppl 1

pub_type

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