Interaction of Interleukin‐1 and Interferon‐γ on Fibroblast Growth Factor‐induced Angiogenesis

Wiley - Tập 85 Số 5 - Trang 522-529 - 1994
K Norioka1, Toshihiro Mitaka1, Yohichi Mochizuki1, Masako Hara2,3, Mitsuhiro Kawagoe2, Haruo Nakamura2
1Department of Pathology, Cancer Research Institute, Sapporo Medical University, School of Medicine, South 1, West 17, Chuo-ku, Sapporo 060
2First Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa 359
3Institute of Rheumatology, Tokyo Women's Medical College, KS Bldg., 9-12 Wakamatsu-cho, Shinjuku-ku, Tokyo 162.

Tóm tắt

The interaction of interleukin‐1 (IL‐1) and interferon‐γ (IFN‐γ) actions on several aspects of angiogenesis in vitro and in vivo was studied. The proliferation and migration of human umbilical vein endothelial cells cultured with basic fibroblast growth factor (bFGF) were synergistically inhibited by cotreatment with IL‐1 and IFN‐γ. Endothelial cell adhesion to collagen was suppressed by IL‐1 and the effect was slightly enhanced by the combination of IL‐1 and IFN‐γ. Local administration of IL‐1 (10,000 U) and IFN‐γ (1,000 U) inhibited bFGF‐induced angiogenesis in the skin of mice, and synergistic inhibitory activity of the combination was demonstrated. Expression of FGF receptors was strongly downregulated by the combination, whereas expressions of epidermal growth factor (EGF) receptors, integrin β1 and integrin β3 were not. EGF partially abrogated the growth‐inhibitory effects of IL‐1 and IFN‐γ. These findings indicate that IL‐1 and IFN‐γ are each able to act an angiogenesis inhibitor in a situation where FGF plays a major role in angiogenesis, and the activity is synergistically enhanced when they are used in combination.

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