Recombinant human erythropoietin reduces epithelial cell apoptosis and attenuates bleomycin-induced pneumonitis in mice.
OBJECTIVE
Erythropoietin (EPO) has recently been demonstrated to have a tissue protective role by acting as an anti-apoptotic agent in various tissues, such as brain, spinal cord, heart and kidney. The purpose of this study was to determine whether human recombinant EPO reduces epithelial cell apoptosis and attenuates bleomycin-induced pneumonitis in mice.


METHODS
Bleomycin was instilled intratracheally into C57BL/6 mice. Recombinant human EPO or saline was injected intraperitoneally, daily from day 5 to day 13 after bleomycin instillation.


RESULTS
EPO receptor was expressed in bronchiolar and alveolar type II cells. At 14 days after instillation, the number of terminal uridine deoxynucleotidyl transferase nick end-labelled positive cells in the lung was decreased, and the histological degree of inflammation and fibrosis was attenuated in mice injected with EPO compared with controls. Expression of phosphorylated Akt and Erk, which are thought to mediate the survival signalling pathway induced by EPO, tended to be increased in lung tissues from mice treated with EPO compared with those from mice treated with saline after bleomycin instillation.


CONCLUSIONS
As it is likely that EPO protects epithelial cells from injury and apoptosis, EPO administration could be a potential therapeutic strategy for the prevention of lung injury.
Yoshimi
Michihiro
M
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Maeyama
Takashige
T
Yamada
Mizuho
M
Hamada
Naoki
N
Fukumoto
Jyutaro
J
Kawaguchi
Tomonobu
T
Kuwano
Kazuyoshi
K
Nakanishi
Yoichi
Y
D000818:Animals; D000903:Antibiotics, Antineoplastic; D017209:Apoptosis / Q000187:drug effects*; D001761:Bleomycin; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D004921:Erythropoietin / Q000494:pharmacology* / Q000627:therapeutic use; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D017467:Receptors, Erythropoietin / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology* / Q000627:therapeutic use
D000903:Antibiotics, Antineoplastic; D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D001761:Bleomycin; D004921:Erythropoietin; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases