IL-13 stimulates vascular endothelial cell growth factor and protects against hyperoxic acute lung injury.
Hyperoxia is an important cause of acute lung injury. To determine whether IL-13 is protective in hyperoxia, we compared the survival in 100% O(2) of transgenic mice that overexpress IL-13 in the lung and of nontransgenic littermate controls. IL-13 enhanced survival in 100% O(2). One hundred percent of nontransgenic mice died in 4-5 days, whereas 100% of IL-13-overexpressing mice lived for more than 7 days, and many lived 10-14 days. IL-13 also stimulated VEGF accumulation in mice breathing room air, and it interacted with 100% (2) to increase VEGF accumulation further. The 164-amino acid isoform was the major VEGF moiety in bronchoalveolar lavage from transgenic mice in room air, whereas the 120- and 188-amino acid isoforms accumulated in these mice during hyperoxia. In addition, antibody neutralization of VEGF decreased the survival of IL-13-overexpressing mice in 100% (2). These studies demonstrate that IL-13 has protective effects in hyperoxic acute lung injury. They also demonstrate that IL-13, alone and in combination with 100% (2), stimulates pulmonary VEGF accumulation, that this stimulation is isoform-specific, and that the protective effects of IL-13 are mediated, in part, by VEGF.
Corne
J
J
Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Chupp
G
G
Lee
C G
CG
Homer
R J
RJ
Zhu
Z
Z
Chen
Q
Q
Ma
B
B
Du
Y
Y
Roux
F
F
McArdle
J
J
Waxman
A B
AB
Elias
J A
JA
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000032:analysis; D018496:Hyperoxia / Q000378:metabolism* / Q000473:pathology*; D007150:Immunohistochemistry; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008222:Lymphokines / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009130:Muscle, Smooth / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000906:Antibodies; D016228:Endothelial Growth Factors; C496454:Fgf7 protein, mouse; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D018793:Interleukin-13; D008222:Lymphokines; D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D010100:Oxygen