[Effects of granulocyte-macrophage colony stimulating factor on nuclear factor-KappaB activation in multiple organs of hemorrhage-induced acute lung injury in mice].

Abstract

OBJECTIVE:

To investigate the effects of nuclear factor-KappaB (NF-KappaB) activation in multiple organs of hemorrhage-induced acute lung injury (ALI) by the specific granulocyte-macrophage colony stimulating factor (GM-CSF)-neutralizing antibody (22E9) and dexamethasone (DEX) in mice.

METHODS:

Twenty male C57BL/6 mice were used to reproduce a model of hemorrhagic shock by cardiac puncture. Before cardiac puncture, mice in different groups were transnasally administered with phosphate buffered solution (PBS, PCG group), PBS plus 1 microg 22E9 (HS1 group), PBS plus 10 microg 22E9 (HS10 group) and PBS plus 20 microg DEX (DEX group), respectively. In negative control group (NCG group) received cardiac puncture without shock followed by transnasal administration with PBS without shock. Lungs, hearts, livers and kidneys tissues of mice were harvested at 4 hours after hemorrhagic shock. The activities of NF-KappaB in different organs was determined by electrophoretic mobility shift assay (EMSA). The tumor necrosis factor-alpha (TNF-alpha) in lung and heart were determined by enzyme-linked immunosorbent assay (ELISA).

RESULTS:

22E9 in both low or high doses could significantly inhibit NF-KappaB activities in lung, heart and liver, and elevated NF-KappaB activity in kidney compared with those of PCG group (all P<0.05). The effect of 22E9 was much better in HS1 group than in HS10 group (all P<0.05). DEX significantly strengthened NF-KappaB activity in kidney (P<0.05) and didn't significantly inhibit NF-KappaB activities in heart and liver compared with those of PCG group. 22E9 significantly inhibited TNF-alpha in lung and heart, while DEX significantly inhibited TNF-alpha in heart (all P<0.05).

CONCLUSION:

22E9 can inhibit the NF-KappaB activation and inflammatory reaction in multiple organs after hemorrhage-induced ALI and reduce injury in multiple organs, while DEX has no significant effect.

• Authors: Qian Wang, Yong Song, Yi Shi
• Journal: Zhongguo wei zhong bing ji jiu yi xue = Chinese critical care medicine = Zhongguo weizhongbing jijiuyixue (Zhongguo Wei Zhong Bing Ji Jiu Yi Xue) Vol. 19 Issue 5 Pg. 295-8 (May 2007) ISSN: 1003-0603 [Print] China
• PMID: 17490571 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies
• NF-kappa B
• Tumor Necrosis Factor-alpha
• Dexamethasone
• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Acute Lung Injury (etiology, metabolism)
• Animals
• Antibodies (pharmacology)
• Dexamethasone (pharmacology)
• Disease Models, Animal
• Granulocyte-Macrophage Colony-Stimulating Factor (immunology, physiology)
• Male
• Mice
• Mice, Inbred C57BL
• NF-kappa B (metabolism)
• Random Allocation
• Shock, Hemorrhagic (complications, metabolism)
• Tumor Necrosis Factor-alpha (metabolism)