Granulocyte Colony Stimulating Factor Attenuates Hyperoxia-Induced Lung Injury by Down-Modulating Inflammatory Responses in Neonatal Rats.
- Author:
Ga Won JEON
1
;
Dong Kyung SUNG
;
Yu Jin JUNG
;
Soo Hyun KOO
;
Seo Heui CHOI
;
Yun Sil CHANG
;
Jong Beom SIN
;
Won Soon PARK
Author Information
- Publication Type:Original Article
- Keywords: Granulocyte colony stimulating factor; bronchopulmonary dysplasia; inflammation; animals; infant; newborn
- MeSH: Animals; Animals, Newborn; Blotting, Western; Female; Granulocyte Colony-Stimulating Factor/*therapeutic use; Hyperoxia/*complications; In Situ Nick-End Labeling; Interleukin-6/genetics; Lung/*drug effects/*metabolism; Lung Injury/*drug therapy/etiology/genetics/metabolism; NADPH Oxidase/metabolism; Peroxidase/metabolism; Pregnancy; Random Allocation; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Transforming Growth Factor beta/genetics; Tumor Necrosis Factor-alpha/genetics; Weight Gain/drug effects
- From:Yonsei Medical Journal 2011;52(1):65-73
- CountryRepublic of Korea
- Language:English
- Abstract: PURPOSE: Granulocyte colony stimulating factor (G-CSF) has been known to increase neutrophil production and have anti-inflammatory properties, but the effect of G-CSF on pulmonary system is in controversy. We investigated whether G-CSF treatment could attenuate hyperoxia-induced lung injury, and whether this protective effect is mediated by the down-modulation of inflammatory responses in a neonatal rat model. MATERIALS AND METHODS: Newborn Sprague-Dawley rats (Orient Co., Seoul, Korea) were subjected to 14 days of hyperoxia (90% oxygen) beginning within 10 h after birth. G-CSF (20 microg/kg) was administered intraperitoneally on the fourth, fifth, and sixth postnatal days. RESULTS: This treatment significantly improved hyperoxia-induced reduction in body weight gain and lung pathology such as increased mean linear intercept, mean alveolar volume, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling positive cells. Hyperoxia-induced activation of nicotinamide adenine dinucleotide phosphate oxidase, which is responsible for superoxide anion production, as evidenced by upregulation and membrane translocation of p67phox was significantly attenuated after G-CSF treatment, as were inflammatory responses such as increased myeloperoxidase activity and mRNA expression of transforming growth factor-beta. However, the attenuation of other proinflammatory cytokines such as tumor necrosis factor-alpha and interleukin-6 was not significant. CONCLUSION: In sum, G-CSF treatment significantly attenuated hyperoxia-induced lung injury by down-modulating the inflammatory responses in neonatal rats.
