Inhibition of c-Jun NH2-terminal kinase or extracellular signal-regulated kinase improves lung injury

Respiratory Research

Jihee Lee Kang¹  Young Hae Chong²  Chang Sook Moon¹  Hee Jae Kim¹  Hui Su Lee¹ 

[1] Department of Physiology, Division of Cell Biology, Ewha Medical Research Institute, Ewha Womans University College of Medicine, 911-1 Mok-6-dong, Yangcheon-ku, Seoul 158-056, Korea;Department of Microbiology, Division of Cell Biology, Ewha Medical Research Institute, Ewha Womans University College of Medicine, 911-1 Mok-6-dong, Yangcheon-ku, Seoul 158-056, Korea

关键词: NF-κB;    acute lung injury;    LPS;    ERK;    JNK;   

Others  :  1227353
DOI  :  10.1186/1465-9921-5-23

 received in 2004-08-27, accepted in 2004-11-27,  发布年份 2004

【 摘 要 】

Background

Although in vitro studies have determined that the activation of mitogen-activated protein (MAP) kinases is crucial to the activation of transcription factors and regulation of the production of proinflammatory mediators, the roles of c-Jun NH₂-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) in acute lung injury have not been elucidated.

Methods

Saline or lipopolysaccharide (LPS, 6 mg/kg of body weight) was administered intratracheally with a 1-hour pretreatment with SP600125 (a JNK inhibitor; 30 mg/kg, IO), or PD98059 (an MEK/ERK inhibitor; 30 mg/kg, IO). Rats were sacrificed 4 hours after LPS treatment.

Results

SP600125 or PD98059 inhibited LPS-induced phosphorylation of JNK and ERK, total protein and LDH activity in BAL fluid, and neutrophil influx into the lungs. In addition, these MAP kinase inhibitors substantially reduced LPS-induced production of inflammatory mediators, such as CINC, MMP-9, and nitric oxide. Inhibition of JNK correlated with suppression of NF-κB activation through downregulation of phosphorylation and degradation of IκB-α, while ERK inhibition only slightly influenced the NF-κB pathway.

Conclusion

JNK and ERK play pivotal roles in LPS-induced acute lung injury. Therefore, inhibition of JNK or ERK activity has potential as an effective therapeutic strategy in interventions of inflammatory cascade-associated lung injury.

【 授权许可】

   
2004 Lee et al; licensee BioMed Central Ltd.

【 图 表 】

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