Activation of c-Jun N-terminal kinase (JNK) signalling in experimentally induced gastric lesions in rats.
The c-Jun N-terminal kinase (JNK) participates in intracellular signalling cascades that mediate inflammatory responses. Therefore, the JNK signalling may be involved in gastric injury and inhibition of this pathway may form the basis of a new strategy for the treatment of gastric injury. The aim of this study was to determine whether JNK participates in the formation of gastric lesions in an experimental model. Acute gastric injury was induced in Sprague-Dawley rats by intragastric administration of 100% ethanol. The amount of phospho-JNK in the rat stomach was determined using immunohistochemistry and Western analysis. Animals received subcutaneous injections of a specific JNK inhibitor SP600125 or vehicle and the extent of mucosal damage in the stomach was determined. Western analysis revealed early phosphorylation of JNK and, to a lesser extent, p38 as well as late phosphorylation of the p42/44 extracellular signal-related kinases during the development of gastric lesions. JNK was phosphorylated in epithelial cells and in occasional mononuclear cells present at lesion sites. These cells were rarely found in samples from control specimens. Treatment with SP600125 significantly reduced the extent of gastric lesions. These findings indicate that experimental gastric injury is associated with activation of the JNK signalling pathway, and also suggest that JNK inhibitors may play a role in the treatment of gastric injury in humans.
Mitsuyama
K
K
Second Department of Medicine, Kurume University School of Medicine, Kurume, Japan. ibd@med.kurume-u.ac.jp
Tsuruta
O
O
Matsui
Y
Y
Harada
K
K
Tomiyasu
N
N
Suzuki
A
A
Takaki
K
K
Masuda
J
J
Handa
K
K
Satoh
Y
Y
Bennett
B L
BL
Toyonaga
A
A
Sata
M
M
D000818:Animals; D000873:Anthracenes / Q000627:therapeutic use; D015153:Blotting, Western / Q000379:methods; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D000431:Ethanol; D048049:Extracellular Signal-Regulated MAP Kinases / Q000032:analysis; D005260:Female; D005753:Gastric Mucosa / Q000201:enzymology* / Q000473:pathology; D005756:Gastritis / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control; D007150:Immunohistochemistry / Q000379:methods; D048031:JNK Mitogen-Activated Protein Kinases / Q000032:analysis* / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000032:analysis
D000873:Anthracenes; D004791:Enzyme Inhibitors; C432165:pyrazolanthrone; D000431:Ethanol; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases