Journal of Molecular Medicine

, Volume 85, Issue 6, pp 635–645 | Cite as

Local administration of WIN 55,212-2 reduces chronic granuloma-associated angiogenesis in rat by inhibiting NF-κB activation

  • Daniele De Filippis
  • Annapina Russo
  • Daniela De Stefano
  • Maria Chiara Maiuri
  • Giuseppe Esposito
  • Maria Pia Cinelli
  • Concetta Pietropaolo
  • Rosa Carnuccio
  • Giulia Russo
  • Teresa Iuvone
Original Article


Chronic inflammation is often associated with granuloma formation that is a hallmark of many human diseases. The transcription factor nuclear factor-kappa B (NF-κB) plays a central role in this process by regulating the expression of several pro-inflammatory genes. Cannabinoids (CBs) from Cannabis sativa L. exert a large number of biological effects including anti-inflammatory and anti-angiogenic effects. In this study, we investigated the role of CBs on granuloma formation induced by λ-carrageenin-soaked sponge implant in rat. Our results show that local administration of WIN 55,212-2, a CB1/CB2 agonist, given daily or at time of implantation significantly decreased weight and neo-angiogenesis in granuloma tissue and inhibited nuclear factor-kappa B (NF-κB)/DNA binding that was associated with a reduced inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), tumor necrosis factor alpha (TNF-α), and vascular endothelial growth factor (VEGF) messenger RNA (mRNA) and protein expression. Also, arachidonyl-2-chloroethylamide (ACEA), a CB1 selective agonist, and JWH-015, a CB2 selective agonist, exhibited the same effects that were reversed by SR141716-A and SR144528, respectively, CB1 and CB2 selective antagonists. These results indicate that CBs given locally may represent a potential therapeutic tool in controlling chronic inflammation avoiding psychotropic effects.


Cannabinoids Chronic inflammation Angiogenesis Nuclear factor-kappa B 


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Daniele De Filippis
    • 1
  • Annapina Russo
    • 2
  • Daniela De Stefano
    • 1
  • Maria Chiara Maiuri
    • 1
  • Giuseppe Esposito
    • 1
  • Maria Pia Cinelli
    • 3
  • Concetta Pietropaolo
    • 2
  • Rosa Carnuccio
    • 1
  • Giulia Russo
    • 2
  • Teresa Iuvone
    • 1
  1. 1.Dipartimento di Farmacologia SperimentaleUniversità degli Studi di Napoli “Federico II”NapoliItaly
  2. 2.Dipartimento di Biochimica e Biotecnologie MedicheUniversità degli Studi di Napoli “Federico II”NapoliItaly
  3. 3.Dipartimento di Scienze BiomorfologicheUniversità degli Studi di Napoli “Federico II”NapoliItaly

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