Th1-derived cytokine IFN-gamma is a potent inhibitor of eotaxin synthesis in vitro.
Eotaxin potentially plays an integral role in tissue eosinophilia. Inasmuch as Th2-derived cytokine IL-4 has been shown to stimulate eotaxin generation, we investigated here the effect of Th1-derived cytokine IFN-gamma on human eotaxin production. IFN-gamma but not -alpha or -beta potently inhibited tumor necrosis factor (TNF)-alpha-induced eotaxin generation by dermal fibroblasts. The inhibitory effect was unique to eotaxin, because production of IL-8 or monocyte chemoattractant protein (MCP)-1 protein was not affected by the treatment with IFN-gamma. Furthermore, the suppressive effect of IFN-gamma was not cell-type or stimulus specific. The level of eotaxin mRNA increased within 2 h after activation with TNF-alpha and continued to increase up to 72 h. IFN-gamma did not inhibit, but rather augmented the TNF-alpha-induced accumulation of mRNA in the early phase ( approximately 6 h). However, in the later phase, IFN-gamma completely prevented the subsequent elevation of eotaxin mRNA and sustained it at low levels. Although the protective effect of IFN-gamma against allergic inflammation has been assumed to result from its sole regulation of the proliferation of Th2-type T lymphocytes, these results imply that IFN-gamma can also directly act on stromal cells to inhibit eotaxin production and consequently intervene in eosinophil recruitment.
Miyamasu
M
M
Department of Allergy and Rheumatology, CREST, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Yamaguchi
M
M
Nakajima
T
T
Misaki
Y
Y
Morita
Y
Y
Matsushima
K
K
Yamamoto
K
K
Hirai
K
K
D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D004306:Dose-Response Relationship, Immunologic; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D012867:Skin / Q000166:cytology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
C515456:CCL11 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma