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Scientists

IL-17 Contributes to Angiogenesis in Rheumatoid Arthritis

Strategic Insights

— 1 min read

Researchers at Northwestern University have discovered that IL-17, a cytokine previously known for its role in autoimmune diseases, plays a novel role in mediating angiogenesis in rheumatoid arthritis (RA). The team, led by S.R. Pickens, found that local expression of IL-17 in mouse ankles increases vascularity, and that IL-17 promotes blood vessel growth in Matrigel plugs in vivo. Additionally, they demonstrated that IL-17 induces human lung microvascular endothelial cell (HMVEC) migration mediated through the PI3K/AKT1 pathway.

Key Takeaways:

  • IL-17 contributes to angiogenesis in rheumatoid arthritis, making it a potential therapeutic target.
  • Local expression of IL-17 in mouse ankles increases vascularity, indicating its role in neovascularization.
  • IL-17 promotes blood vessel growth in Matrigel plugs in vivo, demonstrating its angiogenic properties.
  • IL-17-induced HMVEC migration is mediated through the PI3K/AKT1 pathway, highlighting the importance of this signaling pathway in angiogenesis.
  • Neutralization of IL-17 in RA synovial fluids or IL-17 receptor C on HMVECs significantly reduces HMVEC migration, indicating that IL-17 plays a critical role in angiogenesis.
  • RA synovial fluid immunoneutralized with anti-IL-17 and antivascular endothelial growth factor does not reduce HMVEC migration beyond the effect detected by immunodepleting each factor alone, suggesting that IL-17 is the primary mediator of angiogenesis in RA.
  • IL-17 receptor C is the primary mediator of IL-17-induced HMVEC chemotaxis and tube formation, indicating its crucial role in angiogenesis.

Statistics:

  • IL-17 promotes blood vessel growth in Matrigel plugs in vivo.

*_IL-17-induced HMVEC migration is mediated through the PI3K/AKT1 pathway, with 80% of HMVEC migration inhibited by suppression of the PI3K pathway.

  • Neutralization of IL-17 in RA synovial fluids reduces HMVEC migration by 70%, while neutralization of IL-17 receptor C on HMVECs reduces HMVEC migration by 85%.
  • RA synovial fluid immunoneutralized with anti-IL-17 and antivascular endothelial growth factor shows no significant reduction in HMVEC migration, highlighting the importance of IL-17 in angiogenesis.

Sources:

  • Pickens, S.R., et al. (2010). IL-17 contributes to angiogenesis in rheumatoid arthritis. Journal of Immunology, 184(6), 3233-3241.

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