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作者

Wang, Z. Chen, D. Zhang, R. An, S. Zhang, Z. Ma, Q.

作者单位

Department of Anatomy, Taishan Medical University, Taian 271000, Shandong Province, China

刊名

Neurochemical Research

年份

2013

卷号

Vol.38 No.9

页码

1895-1903

ISSN

0364-3190;1573-6903

关键词

Interleukin-1β Pain modulation Primary sensory neurons Protease-activated receptor-4 Protein kinase C

摘要

Protease-activated receptor-4 is localized in primary sensory neurons and is believed to implicate in the modulation of nociceptive mechanisms. The pro-inflammatory cytokine interleukin-1β is involved in the generation of hyperalgesia in pathological states such as neuropathy and inflammation. Previous studies have shown that IL-1β enhances the expression of PAR4 in many cell types but the effect of this cytokine on primary sensory neuron PAR4 expression is less clear. In the present study, we...更多

Protease-activated receptor-4 is localized in primary sensory neurons and is believed to implicate in the modulation of nociceptive mechanisms. The pro-inflammatory cytokine interleukin-1β is involved in the generation of hyperalgesia in pathological states such as neuropathy and inflammation. Previous studies have shown that IL-1β enhances the expression of PAR4 in many cell types but the effect of this cytokine on primary sensory neuron PAR4 expression is less clear. In the present study, we evaluated in rat dorsal root ganglion neurons the influence of IL-1β on PAR4 mRNA and protein levels after IL-1β intraplantar injection into the hind-paw or treatment of cultured DRG neurons. The expression of PAR4 in cultured DRG neurons was also assessed after treatment with IL-1β with pre-addition of phorbol-12-myristate 13-acetate or chelerythrine chloride . We found that IL-1β intraplantar injection into the hind-paw or long-term exposure of cultured DRG neurons to IL-1β significantly increased the proportion of DRG neurons expressing PAR4 immunoreactivity. Real-time PCR and western blotting showed that IL-1β treatment also significantly elevated PAR4 mRNA and protein levels in DRG neurons. This IL-1β effect was enhanced in DRG neurons when DRG cultures were pre-treatment with the PMA. But pre-incubation with chelerythrine chloride strongly inhibited the IL-1β-induced increase of PAR4 mRNA and protein levels. These results demonstrate that the expression of PAR4 mRNA and protein induced by IL-1β is PKC signaling pathway dependent.收起

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