Acetylcholine Regulation of Synoviocyte Cytokine Expression by the Alpha7 Nicotinic Receptor

Strategic Insights -

Scientists in the United States have made a significant breakthrough in understanding the regulation of inflammation in rheumatoid arthritis (RA) through the cholinergic pathway. This pathway is mediated by the neurotransmitter acetylcholine (ACh), which can bind to the alpha7 cholinergic receptor (alpha7R) expressed by nonneuronal cells. Research findings suggest that ACh can reduce inflammation by inhibiting cytokine expression in fibroblast-like synoviocytes (FLS), a type of cell found in the synovium, the tissue that surrounds joints. The study, published in Arthritis and Rheumatism, also identifies the alpha7 receptor as a potential therapeutic target for inflammatory diseases.

Key Takeaways:

  • The alpha7 nicotinic receptor is expressed in the synovium and by synoviocytes, and receptor ligation inhibits cytokine expression in FLS through a posttranscriptional mechanism.
  • Acetylcholine (ACh) significantly reduces the production of IL-6, CXCL8, CCL2, CCL3, CCL5, and granulocyte colony-stimulating factor by interleukin-1 (IL-1)-stimulated FLS.
  • The alpha7R antagonist methyllycaconitine (MLA) or the use of alpha7R siRNA to knock down receptor expression blocked the effects of ACh.
  • The selective alpha7R agonist PNU-282,987 decreased the production of IL-6 by IL-1-stimulated FLS.
  • The alpha7 receptor is a potential therapeutic target for inflammatory diseases.

Statistics:

  • 6 cytokines (IL-6, CXCL8, CCL2, CCL3, CCL5, and granulocyte colony-stimulating factor) were reduced by ACh stimulation in IL-1-stimulated FLS.
  • 11.8% reduction in IL-6 production was observed in FLS treated with PNU-282,987.
  • 89% reduction in CXCL8 production was observed in FLS treated with ACh.
  • 85% reduction in CCL2 production was observed in FLS treated with ACh.

Sources:

  • Waldburger, J.M. et al. (2008). Acetylcholine regulation of synoviocyte cytokine expression by the alpha7 nicotinic receptor. Arthritis and Rheumatism, 58(11), 3439-3449.
  • Publisher contact information for the journal Arthritis and Rheumatism: Wiley-Liss, Division John Wiley & Sons Inc., 111 River St., Hoboken, NJ 07030, USA.