Bleomycin-induced lung fibrosis in IL-4-overexpressing and knockout mice.
The role of IL-4 in the development of lung fibrosis is as yet unclear. Bleomycin (Bleo) or saline (Sal) was injected intratracheally into three groups of C57BL/6J mice: transgenic animals that overexpressed IL-4 (IL-4 TG, n = 14), mice with a targeted knockout mutation of the IL-4 gene (IL-4 KO, n = 11), and wild-type (WT, n = 13) mice. At 14 days, lung fibrosis was evaluated by hydroxyproline measurement and by quantitative image analysis of fibrosis fraction and alveolar wall area fraction. Bronchoalveolar lavage cell counts in all Bleo-treated groups demonstrated an increased percentage of lymphocytes with a corresponding decrease in the percentage of macrophages. Comparing Bleo- to Sal-treated controls within each group of mice showed increases in all lung fibrosis parameters in IL-4 KO and WT, but not in any of the parameters in IL-4 TG mice. The severity of Bleo-induced fibrotic response was decreased in overexpressed IL-4 TG compared with IL-4 KO mice. These data negate a critical profibrotic role for IL-4 in Bleo-induced lung fibrosis.
Izbicki
Gabriel
G
Lung Cellular and Molecular Biology Laboratory, Institute of Pulmonology, Hadassah University Hospital and The Hebrew University-Hadassah Medical School, 91120 Jerusalem, Israel.
Or
Reuven
R
Christensen
Thomas G
TG
Segel
Michael J
MJ
Fine
Alan
A
Goldstein
Ronald H
RH
Breuer
Raphael
R
D000818:Animals; D001761:Bleomycin / Q000633:toxicity*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D006909:Hydroxyproline / Q000378:metabolism; D015847:Interleukin-4 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000502:physiology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011650:Pulmonary Alveoli / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001761:Bleomycin; D015847:Interleukin-4; D006909:Hydroxyproline