Canna~Fangled Abstracts

Activation of cannabinoid receptor 2 attenuates synovitis and joint distruction in collagen-induced arthritis.

By December 30, 2014 No Comments
2014 Dec 30. pii: S0171-2985(14)00281-2. doi: 10.1016/j.imbio.2014.12.012. [Epub ahead of print]
Gui H1, Liu X2, Liu LR3, Su DF4, Dai SM5.

Abstract

OBJECTIVES:

pm1Recent studies have suggested immunomodulatory and anti-inflammatory effects of cannabinoid receptor 2 (CB2R) activation, which is devoid of psychoactivity. We have demonstrated the expression of CB2R in synovial tissue from patients with rheumatoid arthritis (RA), and its specific activation shows inhibitory effects on fibroblast-like synoviocytes. However, it is still unclear whether selective activation of CB2R inhibits joint inflammation or protects joint damage in RA.

METHODS:

A murine model of collagen-induced arthritis (CIA) was used to evaluate the therapeutic efficacy of HU-308, a selective CB2R agonist. The disease severity was evaluated by semi-quantitative scoring of joint swelling, histological assessment of joint inflammation and structure, and radiographic assessment of joint destruction by using digital plain radiographs and micro-CT scans. The concentrations of various isotypes of anti-collagen II antibodies in sera and the levels of cytokines in culture supernatants were determined by ELISA.

RESULTS:

Compared with vehicle treatment, protective treatment with intraperitoneal injection of HU-308 (0.3-1.0mg/kg) failed to decrease the incidence of the development of CIA, but it effectively suppressed the severity of the disease. In CIA mice, treatment with HU-308 significantly decreased joint swelling, synovial inflammation, and joint destruction, as well as serum levels of anti-collagen II antibodies. In vitro, HU-308 (1-10μM) significantly suppressed the production of proinflammatory cytokines IL-6 and TNF-α from lipopolysaccharide-stimulated murine peritoneal macrophages with intact CB2R in dose-dependent manners. HU-308 failed to elicit any inhibitory effect of on lipopolysaccharide-stimulated macrophages from CB2R-knockout mice.

CONCLUSIONS:

Activation of CB2R by HU-308 has therapeutic potential for RA to suppress synovitis and alleviate joint destruction by inhibiting the production of autoantibodies and proinflammatory cytokines.
Copyright © 2014 Elsevier GmbH. All rights reserved.

KEYWORDS:

Cannabinoid receptor 2; Collagen-induced arthritis; Rheumatoid arthritis

PMID:

 

25601571

 

[PubMed – as supplied by publisher]
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