Protective effect of IL-6 on alveolar epithelial cell death induced by hydrogen peroxide.
The goal of this study was to examine whether IL-6 could directly protect lung resident cells, especially alveolar epithelial cells, from reactive oxygen species (ROS)-induced cell death. ROS induced IL-6 gene expression in organotypic lung slices of wild-type (WT) mice. ROS also induced IL-6 gene expression in mouse primary lung fibroblasts, dose dependently. The organotypic lung slices of WT were more resistant to ROS-induced DNA fragmentation than those of IL-6-deficient (IL-6-/-) mice. WT resistance against ROS was abrogated by treatment with anti-IL-6 antibody. TdT-mediated dUTP nick end labeling stain and electron microscopy revealed that DNA fragmented cells in the IL-6-/- slice included alveolar epithelial cells and endothelial cells. In vitro studies demonstrated that IL-6 reduced ROS-induced A549 alveolar epithelial cell death. Together, these data suggest that IL-6 played an antioxidant role in the lung by protecting lung resident cells, especially alveolar epithelial cells, from ROS-induced cell death.
Kida
Hiroshi
H
National Hospital Organization Japan, Osaka Minami Medical Center, Kawachinagano, Osaka, Japan.
Yoshida
Mitsuhiro
M
Hoshino
Shigenori
S
Inoue
Koji
K
Yano
Yukihiro
Y
Yanagita
Masahiko
M
Kumagai
Toru
T
Osaki
Tadashi
T
Tachibana
Isao
I
Saeki
Yukihiko
Y
Kawase
Ichiro
I
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019610:Cytoprotection; D053938:DNA Fragmentation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D016877:Oxidants; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide