Abstract
Aim:
Interleukin-1 beta (IL-β) 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-1β after SCI, we examined the expression of IL-1β, 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-1β.
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-1β, 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-β 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.
Conclusion:
The p38MAPK signaling pathway plays an important role in IL-1β mediated induction of neuron apoptosis following SCI in rats.
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Project supported by grants from the Natural Science Foundation of Guangdong Province, China (No 013216), and the Foundation of Guangdong Health Bureau, China (No A2003521).
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Wang, Xj., Kong, Km., Qi, Wl. et al. Interleukin-1 beta induction of neuron apoptosis depends on p38 mitogen-activated protein kinase activity after spinal cord injury. Acta Pharmacol Sin 26, 934–942 (2005). https://doi.org/10.1111/j.1745-7254.2005.00152.x
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DOI: https://doi.org/10.1111/j.1745-7254.2005.00152.x
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