Extracellular signal-regulated kinase-mediated IL-1-induced cortical neuron damage during traumatic brain injury.
Traumatic brain injury (TBI) is one of the most prevalent causes of morbidity and mortality in youth. Interleukin-1 (IL-1) has many roles in the brain in addition to mediating glial inflammatory response; it has also been implicated in neurodegenerative diseases. We demonstrated the signal transduction pathway of IL-1 overproduction-induced cortical neuron loss during TBI. A calibrated weight-drop device (450 g weight and 2m height) was used to induce TBI in adult male Sprague-Dawley rats under general anesthesia (sodium pentobarbital: 40 mg/kg, i.p.). Expression of interleukin-1alpha (IL-1alpha), interleukin-1beta (IL-1beta), extracellular signal-regulated kinase (ERK), Jun, and p-38 were determined by Western blotting and RT-PCR. Neuronal damage was evaluated by microscopic examination. We found both mRNA and proteins of cortical IL-1alpha and IL-1beta increased three hours after TBI. Phosphorylation of ERK significantly increased but there were no significant effects on cortical expression of ERK, Jun and p-38. Administration of ERK inhibitor, PD98059, IL-1alpha antibody and IL-1beta antibody protected animals from TBI-induced neuronal damage. Our results suggest that TBI-induced cortical neuron death was mediated by the IL-1 receptor through ERK phosphorylation.
Lu
Kwok-Tung
KT
Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
Wang
Yi-Wen
YW
Wo
Yu-Yuan P
YY
Yang
Yi-Ling
YL
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001930:Brain Injuries / Q000201:enzymology* / Q000276:immunology / Q000503:physiopathology; D016923:Cell Death / Q000502:physiology; D002540:Cerebral Cortex / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008297:Male; D009410:Nerve Degeneration / Q000201:enzymology* / Q000276:immunology / Q000503:physiopathology; D009474:Neurons / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000906:Antibodies; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases