Interleukin-5 suppresses Vascular Endothelial Growth Factor-induced angiogenesis through STAT5 signaling.

Interleukin-5 (IL-5) is best known as key regulator in eosinophil-associated diseases such as asthma. While a connection to vascular changes in eosinophil-associated lung diseases is still elusive, recent evidence suggests that IL-5 may have an atheroprotective role. Here, we report an unexpected anti-angiogenic potential of IL-5 on vascular endothelial cells in vitro. IL-5 significantly inhibited fundamental functions of human lung microvascular endothelial cells (HMVEC-L) in vessel formation including VEGF-induced endothelial cell proliferation, migration and tube formation. Knockdown (KD) of STAT5 abolished the direct anti-angiogenic effect of IL-5 on VEGF-induced endothelial cell proliferation, migration and tube formation.

Inositol 5'-phosphatase, SHIP1 interacts with phospholipase C-gamma1 and modulates EGF-induced PLC activity.

Phospholipase C-gamma1, containing two SH2 and one SH3 domains which participate in the interaction between signaling molecules, plays a significant role in the growth factor-induced signal transduction. However, the role of the SH domains in the growth factor-induced PLC-gamma1 regulation is unclear. By peptide-mass fingerprinting analysis, we have identified SHIP1 as the binding protein for the SH3 domain of PLC-gamma1. SHIP1 was co-immunoprecipitated with PLC-gamma1 and potentiated EGF-induced PLC-gamma1 activation. However, inositol 5'-phosphatase activity of SHIP1 was not required for the potentiation of EGF-induced PLC-gamma1 activation. Taken together, these results suggest that SHIP1 may function as an adaptor protein which can potentiate EGF-induced PLC-gamma1 activation without regards to its inositol 5'-phosphatase activity.