Respiratory Research | |
Inhibition of c-Jun NH2-terminal kinase or extracellular signal-regulated kinase improves lung injury | |
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 |
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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.
【 预 览 】
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