Granulocyte colony stimulating factor attenuates hyperoxia-induced lung injury by down-modulating inflammatory responses in neonatal rats.

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 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.

CONCLUSION:

In sum, G-CSF treatment significantly attenuated hyperoxia-induced lung injury by down-modulating the inflammatory responses in neonatal rats.

• Authors: Ga Won Jeon, Dong Kyung Sung, Yu Jin Jung, Soo Hyun Koo, Seo Heui Choi, Yun Sil Chang, Jong Beom Sin, Won Soon Park
• Journal: Yonsei medical journal (Yonsei Med J) Vol. 52 Issue 1 Pg. 65-73 (Jan 2011) ISSN: 1976-2437 [Electronic] Korea (South)
• PMID: 21155037 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-6
• Transforming Growth Factor beta
• Tumor Necrosis Factor-alpha
• Granulocyte Colony-Stimulating Factor
• Peroxidase
• NADPH Oxidases

Topics

• 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 Oxidases (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)