In vitro effects of IL-17 on angiogenic properties of endothelial cells in relation to oxygen levels.

The aim of this study has been to elucidate how different oxygen levels impact the effects of Interleukin-17 (IL-17) on angiogenic properties of endothelial cells. Two endothelial cell lines, mouse MS-1 and human EA.hy 926, were grown in 20% and 3% O2 and their angiogenic abilities analyzed after IL-17 treatment: proliferation, apoptosis, migration and tubulogenesis. Expression of endothelial nitric oxide synthase (eNOS) and cyclooxygenase-2 (Cox-2) was also measured. Considering EA.hy 926 cell line, hypoxia alone reduced proliferation, survival and migration, but not their ability to form tubules. When cultured at 20% O2 , IL-17 stimulated proliferation, migration and tubulogenesis, whereas a hypoxic environment did not affect their migration and proliferation, but increased their survival and tubulogenic properties. Expression of eNOS and Cox-2 increased by both IL-17 and hypoxia, as well as with their combination. With the MS-1 cell line hypoxia did not affect proliferation, survival, migration and tubule formation. At 20% O2 , IL-17 did not alter their proliferation,but inhibited migration and stimulated tubule formation. At 3% O2 , only the stimulating effect of IL-17 on tubulogenesis was evident. The constitutive expression of eNOS was unaffected by oxygen concentrations or IL-17 supplementation, whereas both IL-17 and hypoxia upregulated Cox-2 expression. Thus the effects of IL-17 on the angiogenic properties of endothelial cells depend on both the cell line used and the oxygen concentration.