Interleukin-17 augments tumor necrosis factor-alpha-induced elaboration of proangiogenic factors from fibroblasts.
Interleukin-17 (IL-17) is a CD4 T cell cytokine. In this report, we investigated the effects of this cytokine on the elaboration of proangiogenic factors by lung fibroblasts. After stimulation with a wide range of doses of IL-17, fibroblasts produced more amount of various kinds of angiogenic factors including NO, HGF, MCP-1, KC, MIP-2, PGE1, PGE2 and VEGF in a dose-dependent manner. Treatment with a COX-1 and COX-2 inhibitor indomethacin did not impair IL-17-induced HGF and VEGF secretion in fibroblasts. In addition, TNF-alpha alone stimulated the elaboration of KC, MIP-2, PGE2 and VEGF in fibroblasts. IL-17 and TNF-alpha in combination up-regulated elaboration of these proangiogenic factors additively or synergistically. Moreover, conditioned media (CM) from IL-17-stimulated fibroblasts showed significantly higher activity on endothelial cell growth than those from non-treated control cells. These results indicate that IL-17 up-regulates elaboration of various proangiogenic factors, and modulates macrophage-derived TNF-alpha-induced production of KC, MIP-2, PGE2 and VEGF by fibroblasts. Our findings also demonstrate that IL-17 might be a potential contributor to the inflammatory angiogenesis via induction of proangiogenic factors by stromal fibroblasts.
Numasaki
Muneo
M
Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan. numasaki77@aol.com
Lotze
Michael T
MT
Sasaki
Hidetada
H
D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D000818:Animals; D017077:Culture Media, Conditioned; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D020381:Interleukin-17 / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D051379:Mice; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D043925:Angiogenesis Inducing Agents; D017077:Culture Media, Conditioned; D016861:Cyclooxygenase Inhibitors; D020381:Interleukin-17; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor; D007213:Indomethacin