Transgenic Overexpression of Interleukin-1β Induces Persistent Lymphangiogenesis But Not Angiogenesis in Mouse Airways

摘要: These studies used bi-transgenic Clara cell secretory protein (CCSP)/IL-1β mice that conditionally overexpress IL-1β in cells to determine whether can promote angiogenesis and lymphangiogenesis airways. Doxycycline treatment induced rapid, abundant, reversible production, influx of neutrophils macrophages, conspicuous persistent lymphangiogenesis, but surprisingly no angiogenesis. Gene profiling showed many up-regulated genes, including chemokines ( Cxcl1, Ccl7 ), cytokines (tumor necrosis factor α, , lymphotoxin-β), leukocyte genes S100A9, Aif1/ Iba1). Newly formed lymphatics persisted after overexpression was stopped. Further examined how IL1R1 receptor activation by lymphangiogenesis. Inactivation vascular endothelial growth (VEGF)-C VEGF-D adeno-associated viral vector-mediated soluble VEGFR-3 (VEGF-C/D Trap) completely blocked showing its dependence on ligands. Consistent with this mechanism, VEGF-C immunoreactivity present some Aif1/Iba1-immunoreactive macrophages. Because contribute IL-1β–induced lung remodeling newborn mice, we their potential role Triple-transgenic CCSP/IL-1β/CXCR2 −/− had the usual IL-1β-mediated neutrophil recruitment, suggesting are not essential. found epithelial basal neuroendocrine cells, these targets IL-1β, detected lymphatics, blood vessels, or leukocytes. We conclude triggered mouse airways is driven VEGF-C/D from not neutrophils, recruited express IL1R1.