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α7 Nicotinic Acetylcholine Receptor is a Novel Mediator of Sinomenine Anti-Inflammation Effect in Macrophages Stimulated by Lipopolysaccharide.

Abstract
Sinomenine (SIN), an alkaloid derived from the plant Sinomenium acutum, has anti-inflammatory and analgesic effects and has been used for rheumatoid arthritis treatment in China. This study aims to verify the hypothesis that SIN acts on α7 nicotinic acetylcholine receptor (α7nAChR) to inhibit the activation of macrophages stimulated by lipopolysaccharide. The prototypical α7nAChR antagonist α-bungarotoxin and mecamylamine attenuated the effect of SIN on tumor necrosis factor-α and interleukin-6 in RAW264.7 murine macrophage-like cells and primary peritoneal macrophages of mouse induced by lipopolysaccharide. With the knockdown of α7nAChR expression in RAW264.7 cells by small interfering RNA, the inhibitory effect of SIN on tumor necrosis factor-α and interleukin-6 was reversed. Sinomenine decreased p65 expression in nuclear and increased IκBα expression in cytoplasm, and these effects were reversed by the α7nAChR small interfering RNA as well. These results indicate that the anti-inflammatory effects of SIN on macrophages in vitro depend on α7nAChR.
AuthorsLang Yi, Jin-Fang Luo, Bing-Bing Xie, Jian-Xin Liu, Jun-Yue Wang, Liang Liu, Pei-Xun Wang, Hua Zhou, Yan Dong
JournalShock (Augusta, Ga.) (Shock) Vol. 44 Issue 2 Pg. 188-95 (Aug 2015) ISSN: 1540-0514 [Electronic] United States
PMID25895149 (Publication Type: Journal Article)
Chemical References
  • Anti-Inflammatory Agents
  • Bungarotoxins
  • I-kappa B Proteins
  • Interleukin-6
  • Lipopolysaccharides
  • Morphinans
  • Nfkbia protein, mouse
  • RNA, Small Interfering
  • Tumor Necrosis Factor-alpha
  • alpha7 Nicotinic Acetylcholine Receptor
  • NF-KappaB Inhibitor alpha
  • sinomenine
  • Mecamylamine
Topics
  • Animals
  • Anti-Inflammatory Agents (chemistry)
  • Bungarotoxins (chemistry)
  • Cytoplasm (metabolism)
  • I-kappa B Proteins (metabolism)
  • Interleukin-6 (metabolism)
  • Lipopolysaccharides (chemistry)
  • Macrophages, Peritoneal (drug effects, metabolism)
  • Male
  • Mecamylamine (chemistry)
  • Mice
  • Mice, Inbred BALB C
  • Morphinans (chemistry)
  • NF-KappaB Inhibitor alpha
  • RAW 264.7 Cells
  • RNA Interference
  • RNA, Small Interfering (metabolism)
  • Tumor Necrosis Factor-alpha (metabolism)
  • alpha7 Nicotinic Acetylcholine Receptor (metabolism)

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