| Abstract | Chronic inflammation is often associated with granuloma formation that is a hallmark of many human diseases. The transcription factor nuclear factor-kappa B (NF-kappaB) 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 lambda-carrageenin-soaked sponge implant in rat. Our results show that local administration of WIN 55,212-2, a CB(1)/CB(2) agonist, given daily or at time of implantation significantly decreased weight and neo-angiogenesis in granuloma tissue and inhibited nuclear factor-kappa B (NF-kappaB)/DNA binding that was associated with a reduced inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), tumor necrosis factor alpha (TNF-alpha), and vascular endothelial growth factor (VEGF) messenger RNA (mRNA) and protein expression. Also, arachidonyl-2-chloroethylamide (ACEA), a CB(1) selective agonist, and JWH-015, a CB(2) selective agonist, exhibited the same effects that were reversed by SR141716-A and SR144528, respectively, CB(1) and CB(2) selective antagonists. These results indicate that CBs given locally may represent a potential therapeutic tool in controlling chronic inflammation avoiding psychotropic effects. |
| Authors | Daniele De Filippis, Annapina Russo, Daniela De Stefano, Maria Chiara Maiuri, Giuseppe Esposito, Maria Pia Cinelli, Concetta Pietropaolo, Rosa Carnuccio, Giulia Russo, Teresa Iuvone
(Affiliation: Dipartimento di Farmacologia Sperimentale, Università degli Studi di Napoli Federico II, Via D. Montesano 49, Napoli, 80131, Italy.)
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| Journal | Journal of molecular medicine (Berlin, Germany)
(J Mol Med)
Vol. 85
Issue 6
Pg. 635-45
(Jun 2007)
ISSN: 0946-2716 Germany |
| PMID | 17447045
(Publication Type: Journal Article)
|
| Chemical References |
- Analgesics
- Benzoxazines
- Morpholines
- NF-kappa B
- Naphthalenes
- Receptors, Cannabinoid
- Win 55212-2
- Carrageenan
|
| Topics |
- Analgesics
(administration & dosage, pharmacology)
- Animals
- Benzoxazines
(administration & dosage, pharmacology)
- Carrageenan
(pharmacology)
- Cell Movement
(drug effects)
- Cell Nucleus
(drug effects, metabolism)
- Gene Expression Regulation
(drug effects)
- Granuloma
(pathology)
- Leukocytes
(cytology, drug effects)
- Male
- Morpholines
(administration & dosage, pharmacology)
- NF-kappa B
(metabolism)
- Naphthalenes
(administration & dosage, pharmacology)
- Neovascularization, Pathologic
- Protein Transport
(drug effects)
- Rats
- Rats, Wistar
- Receptors, Cannabinoid
(agonists, antagonists & inhibitors)
- Time Factors
|
