Title |
Inhibition of c-Jun NH2-terminal kinase or extracellular signal-regulated kinase improves lung injury
|
---|---|
Published in |
Respiratory Research, November 2004
|
DOI | 10.1186/1465-9921-5-23 |
Pubmed ID | |
Authors |
Hui Su Lee, Hee Jae Kim, Chang Sook Moon, Young Hae Chong, Jihee Lee Kang |
Abstract |
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. 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. 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-kappaB activation through downregulation of phosphorylation and degradation of IkappaB-alpha, while ERK inhibition only slightly influenced the NF-kappaB pathway. 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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Russia | 1 | 7% |
Unknown | 13 | 93% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 3 | 21% |
Student > Master | 2 | 14% |
Librarian | 1 | 7% |
Student > Ph. D. Student | 1 | 7% |
Other | 1 | 7% |
Other | 2 | 14% |
Unknown | 4 | 29% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 4 | 29% |
Biochemistry, Genetics and Molecular Biology | 2 | 14% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 7% |
Social Sciences | 1 | 7% |
Medicine and Dentistry | 1 | 7% |
Other | 1 | 7% |
Unknown | 4 | 29% |