title: Interleukin-1 beta induction of neuron apoptosis depends on p38 mitogen-activated protein kinase activity after spinal cord injury.
abstract: OBJECTIVE
  Interleukin-1 beta (IL-1beta) has been implicated as an extracellular signal in the initiation of apoptosis in neurons and oligodendrocytes after spinal cord injury (SCI). To further characterize the apoptotic cascade initiated by IL-1beta after SCI, we examined the expression of IL-1beta, p38 mitogen-activated protein kinase (p38 MAPK) and caspase-3 after SCI, and further investigated whether p38 MAPK was involved in neuron apoptosis induced by IL-1beta.
  
  
  METHODS
  Adult rats were given contusion SCI at the T-10 vertebrae level with a weight-drop impactor (10 g weight dropped 25.0 mm). The expression levels of IL-1beta, p38 MAPK and caspase-3 after SCI were assessed with Western blots, immunohistochemistry staining, and real time reverse transcription polymerase chain reactions (RT-PCR). Neuron apoptosis was assessed with the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) method.
  
  
  RESULTS
  Increased levels of IL-1beta and p38 MAPK were observed soon after injury, with a peak in expression levels within 6 h of injury. By 24 h after injury, caspase-3 expression was markedly increased in the injured spinal cord. TUNEL-positive cells were first observed in the lesioned area 6 h after SCI. The largest number of TUNEL-positive cells was observed at 24 h post-SCI. Intrathecal injection of the IL-1 receptor antagonist IL-1Ra significantly reduced expression of p38 MAPK and caspase-3, and reduced the number of TUNEL-positive cells. Moreover, intrathecal injection of an inhibitor of p38 MAPK, SB203580, also significantly reduced the expression of caspase-3, and reduced the number of TUNEL-positive cells in the injured spinal cord.
  
  
  CONCLUSIONS
  The p38MAPK signaling pathway plays an important role in IL-1beta mediated induction of neuron apoptosis following SCI in rats.
authors.affiliation: Department of Spine Surgery, The Second Affiliated Hospital, Shantou University Medical College, Shantou 515041, China. xj.wang2000@163.com
authors.forename: Xin-jia
authors.initials: XJ
authors.lastname: Wang
authors.forename: Kang-mei
authors.initials: KM
authors.lastname: Kong
authors.forename: Wei-li
authors.initials: WL
authors.lastname: Qi
authors.forename: Wei-lian
authors.initials: WL
authors.lastname: Ye
authors.forename: Pei-song
authors.initials: PS
authors.lastname: Song
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000494:pharmacology; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D007093:Imidazoles; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D011725:Pyridines; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D048051:p38 Mitogen-Activated Protein Kinases; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; C093642:SB 203580