BACKGROUND: IL-4 plays a key role in the induction of allergic inflammation, but its role as an effector molecule is less well-established. Although some observations suggest that IL-4 may mediate increased vascular permeability, which is a characteristic feature of allergic inflammation, evidence for a direct effect on endothelial cell permeability is lacking. OBJECTIVE: To determine the effect of human IL-4 on the albumin permeability of cultured human endothelial cells. METHODS: Human umbilical vein endothelial cells were cultured on permeable membranes and the albumin permeability of endothelial monolayers was measured with and without exposure to recombinant human IL-4. Endothelial cells were exposed to various concentrations of IL-4 (0.001-100 U/mL), for various durations (6-24 h), either in the presence or absence of anti-IL-4 antibody. Recovery of endothelial barrier function following exposure to IL-4 was also examined. RESULTS: IL-4 induced a dose-dependent, reversible increase in endothelial permeability to albumin. Low concentrations of IL-4 (1 U/mL) induced a significant increase in endothelial permeability (P=0.004). IL-4-mediated endothelial leak occurred rapidly, within 6 h of exposure. CONCLUSIONS: IL-4 has the capacity to induce vascular leak by a direct effect on cultured endothelial cells, suggesting a potential effector role for IL-4 in the pathogenesis of vascular leak in allergic diseases.
BACKGROUND:IL-4 plays a key role in the induction of allergic inflammation, but its role as an effector molecule is less well-established. Although some observations suggest that IL-4 may mediate increased vascular permeability, which is a characteristic feature of allergic inflammation, evidence for a direct effect on endothelial cell permeability is lacking. OBJECTIVE: To determine the effect of humanIL-4 on the albumin permeability of cultured human endothelial cells. METHODS:Human umbilical vein endothelial cells were cultured on permeable membranes and the albumin permeability of endothelial monolayers was measured with and without exposure to recombinant humanIL-4. Endothelial cells were exposed to various concentrations of IL-4 (0.001-100 U/mL), for various durations (6-24 h), either in the presence or absence of anti-IL-4 antibody. Recovery of endothelial barrier function following exposure to IL-4 was also examined. RESULTS:IL-4 induced a dose-dependent, reversible increase in endothelial permeability to albumin. Low concentrations of IL-4 (1 U/mL) induced a significant increase in endothelial permeability (P=0.004). IL-4-mediated endothelial leak occurred rapidly, within 6 h of exposure. CONCLUSIONS:IL-4 has the capacity to induce vascular leak by a direct effect on cultured endothelial cells, suggesting a potential effector role for IL-4 in the pathogenesis of vascular leak in allergic diseases.
Authors: Amnah Yamani; David Wu; Lisa Waggoner; Taeko Noah; Anthony J Koleske; Fred Finkelman; Simon P Hogan Journal: J Allergy Clin Immunol Date: 2017-11-17 Impact factor: 10.793
Authors: Christopher D Hammerbeck; Rebecca L Brocato; Todd M Bell; Christopher W Schellhase; Steven R Mraz; Laurie A Queen; Jay W Hooper Journal: J Virol Date: 2016-06-24 Impact factor: 5.103