title: Granulocyte colony stimulating factor attenuates hyperoxia-induced lung injury by down-modulating inflammatory responses in neonatal rats.
abstract: OBJECTIVE
  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.
  
  
  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 μg/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 p67(phox) was significantly attenuated after G-CSF treatment, as were inflammatory responses such as increased myeloperoxidase activity and mRNA expression of transforming growth factor-β. However, the attenuation of other proinflammatory cytokines such as tumor necrosis factor-α and interleukin- 6 was not significant.
  
  
  CONCLUSIONS
  In sum, G-CSF treatment significantly attenuated hyperoxia-induced lung injury by down-modulating the inflammatory responses in neonatal rats.
authors.affiliation: Department of Pediatrics, Pusan Paik Hospital, Inje University College of Medicine, Busan, Korea.
authors.forename: Ga Won
authors.initials: GW
authors.lastname: Jeon
authors.forename: Dong Kyung
authors.initials: DK
authors.lastname: Sung
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Jung
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Koo
authors.forename: Seo Heui
authors.initials: SH
authors.lastname: Choi
authors.forename: Yun Sil
authors.initials: YS
authors.lastname: Chang
authors.forename: Jong Beom
authors.initials: JB
authors.lastname: Sin
authors.forename: Won Soon
authors.initials: WS
authors.lastname: Park
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D018496:Hyperoxia / Q000150:complications*; D020287:In Situ Nick-End Labeling; D015850:Interleukin-6 / Q000235:genetics; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D055370:Lung Injury / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011247:Pregnancy; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D015430:Weight Gain / Q000187:drug effects
chemical_list: D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; D009195:Peroxidase; D019255:NADPH Oxidases