Proto-oncogene tyrosine-protein kinase SRC (Src) inhibition in microglia relieves neuroinflammation in neuropathic pain mouse models
Autor: | Jing Xu, Yuanxing Cai, Qinghao Cheng |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Lipopolysaccharides
Male Proto-Oncogene Proteins pp60(c-src) microglia Bioengineering Applied Microbiology and Biotechnology Cell Line neuroinflammation In vivo medicine Animals Protein kinase A Ligation Protein Kinase Inhibitors Neuroinflammation src Inflammation neuropathic pain Oncogene Microglia Chemistry NF-kappa B General Medicine pp2 Sciatic Nerve Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Hyperalgesia Neuropathic pain Cancer research Neuralgia Tyrosine kinase TP248.13-248.65 Research Article Research Paper Proto-oncogene tyrosine-protein kinase Src Biotechnology |
Zdroj: | Bioengineered, Vol 12, Iss 2, Pp 11390-11398 (2021) Bioengineered article-version (VoR) Version of Record |
ISSN: | 2165-5987 2165-5979 |
Popis: | Chronic neuroinflammation is an important factor in the development of neuropathic pain (NP). Excess microglia activation releases a mass of pro-inflammatory cytokines during neuroinflammation process, leading to a constant painful irritation of the sensory nerve. Src belongs to a non-receptor tyrosine kinase associated with sarcoma, whereas the role of Src in neuropathic pain is controversial. We designed to testify the inflammation-regulatory role of Src in the lipopolysaccharide (LPS)-induced BV2 microglia line and the mouse model of neuropathic pain by partial sciatic nerve ligation (PNL). In BV2 microglia, Src expression was inhibited using a Src family kinase inhibitor PP2 after LPS induced inflammatory response. In vivo, the neuropathic pain in mice was induced by PNL surgery and then treated with PP2. The neuroinflammation level in vitro was detected by enzyme-linked immunosorbent assay (ELISA), immunofluorescence (IF), trans-well and Western blotting (WB) assays, in vivo was examined in PNL mice using immunohistochemistry (IHC) and IF. Finally, mechanical allodynia and thermal hyperalgesia assays were used to access the functional evaluation. Inhibition of Src was decreased microglial inflammation and migration after LPS stimuli. Mechanistically, the expression of nuclear factor kappa B (NF-κB) pathway decreased after Src inhibition. The data in vivo showed that the decrease expression of Src reduced neuroinflammation and the amount of microglia in spinal dorsal horn (SDH), the mechanical allodynia of mice thereby attenuated after Src inhibition. These results indicated that the inhibition of Src took a protective effect in neuropathic pain mouse models via reducing microglia-induced neuroinflammation. |
Databáze: | OpenAIRE |
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