Cannabinoid receptor CB2 is involved in tetrahydrocannabinol-induced anti-inflammation against lipopolysaccharide in MG-63 cells.

Lei Yang,Yin Ding,Yu-Chen Han,Bin Jia,Fei-Fei Li

doi:10.1155/2015/362126

Abstract

Cannabinoid Δ9-tetrahydrocannabinol (THC) is effective in treating osteoarthritis (OA), and the mechanism, however, is still elusive. Activation of cannabinoid receptor CB2 reduces inflammation; whether the activation CB2 is involved in THC-induced therapeutic action for OA is still unknown. Cofilin-1 is a cytoskeleton protein, participating in the inflammation of OA. In this study, MG-63 cells, an osteosarcoma cell-line, were exposed to lipopolysaccharide (LPS) to mimic the inflammation of OA. We hypothesized that the activation of CB2 is involved in THC-induced anti-inflammation in the MG-63 cells exposed to LPS, and the anti-inflammation is mediated by cofilin-1. We found that THC suppressed the release of proinflammatory factors, including tumor necrosis factor α (TNF-α), interleukin- (IL-) 1β, IL-6, and IL-8, decreased nuclear factor-κB (NF-κB) expression, and inhibited the upregulation of cofilin-1 protein in the LPS-stimulated MG-63 cells. However, administration of CB2 receptor antagonist or the CB2-siRNA, not CB1 antagonist AM251, partially abolished the THC-induced anti-inflammatory effects above. In addition, overexpression of cofilin-1 significantly reversed the THC-induced anti-inflammatory effects in MG-63 cells. These results suggested that CB2 is involved in the THC-induced anti-inflammation in LPS-stimulated MG-63 cells, and the anti-inflammation may be mediated by cofilin-1.

Highlights

Oversecretion of proinflammatory factors from osteoblasts plays vital roles in the progress of osteoarthritis [1, 2], and high levels of proinflammatory factors in bones and joints induce pain, cartilage loss, and even joint dysfunction [3, 4]
Coadministration of 0.1 μg/mL doxycycline partially reversed THC-induced decrease of IL-6 and tumor necrosis factor α (TNF-α) release (Figures 6(c)-6(d)). These findings indicated that cofilin-1 was involved in the THCinduced anti-inflammation via CB2 in the MG-63 cells exposed to LPS
Upregulation of cofilin-1 protein partially abolished the THC-induced anti-inflammation (Figure 7). These findings indicated that CB2 receptor is involved in the THCinduced anti-inflammation in the MG-63 cells exposed to LPS, and the anti-inflammation may be mediated by cofilin-1 protein

Summary

Introduction

Oversecretion of proinflammatory factors from osteoblasts plays vital roles in the progress of osteoarthritis [1, 2], and high levels of proinflammatory factors in bones and joints induce pain, cartilage loss, and even joint dysfunction [3, 4]. Reducing the release of proinflammatory factors from osteoblasts is an effective therapy for OA. Long-term use of these drugs brings about many side effects, such as gastritis, gastric ulcer, and/or immune suppression [5, 7]. Cannabinoid Δ9-tetrahydrocannabinol (THC) is a main bioactive component from marijuana [8], and THC is effective in treating OA [9]; the mechanism is still not clear. THC exerts bioactivities by activating cannabinoid receptors [10]. Two main cannabinoid receptors have been discovered, including CB1 and CB2. Activation of CB1 receptor is associated predominantly with a dampening down of neuronal excitability, whereas activation of CB2 receptors is related to reducing immune cell function, including decreases of proinflammatory factors release [11]. We aimed at CB2 receptor, not CB1, as one of the research

Methods

Results

Conclusion