論文

査読有り 国際誌
2015年9月4日

The alternatively spliced fibronectin CS1 isoform regulates IL-17A levels and mechanical allodynia after peripheral nerve injury.

Journal of neuroinflammation
  • Huaqing Liu
  • ,
  • Jennifer Dolkas
  • ,
  • Khan Hoang
  • ,
  • Mila Angert
  • ,
  • Andrei V Chernov
  • ,
  • Albert G Remacle
  • ,
  • Sergey A Shiryaev
  • ,
  • Alex Y Strongin
  • ,
  • Tasuku Nishihara
  • ,
  • Veronica I Shubayev

12
開始ページ
158
終了ページ
158
記述言語
英語
掲載種別
DOI
10.1186/s12974-015-0377-6

BACKGROUND: Mechanical pain hypersensitivity associated with physical trauma to peripheral nerve depends on T-helper (Th) cells expressing the algesic cytokine, interleukin (IL)-17A. Fibronectin (FN) isoform alternatively spliced within the IIICS region encoding the 25-residue-long connecting segment 1 (CS1) regulates T cell recruitment to the sites of inflammation. Herein, we analyzed the role of CS1-containing FN (FN-CS1) in IL-17A expression and pain after peripheral nerve damage. METHODS: Mass spectrometry, immunoblotting, and FN-CS1-specific immunofluorescence analyses were employed to examine FN expression after chronic constriction injury (CCI) in rat sciatic nerves. The acute intra-sciatic nerve injection of the synthetic CS1 peptide (a competitive inhibitor of the FN-CS1/α4 integrin binding) was used to elucidate the functional significance of FN-CS1 in mechanical and thermal pain hypersensitivity and IL-17A expression (by quantitative Taqman RT-PCR) after CCI. The CS1 peptide effects were analyzed in cultured primary Schwann cells, the major source of FN-CS1 in CCI nerves. RESULTS: Following CCI, FN expression in sciatic nerve increased with the dominant FN-CS1 deposition in endothelial cells, Schwann cells, and macrophages. Acute CS1 therapy attenuated mechanical allodynia (pain from innocuous stimulation) but not thermal hyperalgesia and reduced the levels of IL-17A expression in the injured nerve. CS1 peptide inhibited the LPS- or starvation-stimulated activation of the stress ERK/MAPK pathway in cultured Schwann cells. CONCLUSIONS: After physical trauma to the peripheral nerve, FN-CS1 contributes to mechanical pain hypersensitivity by increasing the number of IL-17A-expressing (presumably, Th17) cells. CS1 peptide therapy can be developed for pharmacological control of neuropathic pain.

リンク情報
DOI
https://doi.org/10.1186/s12974-015-0377-6
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/26337825
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4559385
ID情報
  • DOI : 10.1186/s12974-015-0377-6
  • PubMed ID : 26337825
  • PubMed Central 記事ID : PMC4559385

エクスポート
BibTeX RIS