Protective Effect of Resveratrol against IL-1β-Induced Inflammatory Response on Human Osteoarthritic Chondrocytes Partly via the TLR4/MyD88/NF-κB Signaling Pathway: An “in Vitro Study”

Abstract

Resveratrol is a natural polyphenolic compound that prevents inflammation in chondrocytes and animal models of osteoarthritis (OA) via yet to be defined mechanisms. The purpose of this study was to determine whether the protective effect of resveratrol on IL-1β-induced human articular chondrocytes was associated with the TLR4/MyD88/NF-κB signaling pathway by incubating human articular chondrocytes (harvested from osteoarthritis patients) with IL-1β before treatment with resveratrol. Cell viability was evaluated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and TNFα levels in culture supernatants were measured by ELISA(Enzymelinked immunosorbent assay). The levels of TLR4 and its downstream signaling targets (MyD88 and TRAF6) and IL-1β were assessed by measuring the levels of mRNA and protein expression by real-time RT-PCR and western blot analysis, respectively, in addition to assessing NF-κB activation. In addition, TLR4 siRNA was used to block TLR4 expression in chondrocytes further demonstrating that resveratrol prevented IL-1β-mediated inflammation by TLR4 inhibition. We found that resveratrol prevented IL-1β-induced reduction in cell viability. Stimulation of chondrocytes with IL-1β caused a significant up-regulation of TLR4 and its downstream targets MyD88 and TRAF6 resulting in NF-κB activation associated with the synthesis of IL-1β and TNFα. These IL-1β-induced inflammatory responses were all effectively reversed by resveratrol. Furthermore, activation of NF-κB in chondrocytes treated with TLR4 siRNA was significantly attenuated, but not abolished, and exposure to resveratrol further reduced NF-κB translocation. These data suggested that resveratrol prevented IL-1β-induced inflammation in human articular chondrocytes at least in part by inhibiting the TLR4/MyD88/NF-κB signaling pathway suggesting that resveratrol has the potential to be used as a nutritional supplement to counteract OA symptoms.

Schisandrae Fructus Inhibits IL‐1β‐Induced Matrix Metalloproteinases and Inflammatory Mediators Production in SW1353 Human Chondrocytes by Suppressing NF‐κB and MAPK Activation

“…IL‐1β also induces the production of the inflammatory mediators, NO and PGE 2 that play critical roles in the development of OA [Chen et al, ]. Therefore, inhibition of IL‐1β‐induced MMPs and inflammatory mediator production would be beneficial in the treatment of OA [Liu et al, ]. In this study, the production of MMP‐1, MMP‐3, and MMP‐13 was upregulated in SW1353 cells after the stimulation by IL‐1β.…”

The Role of MicroRNAs and Their Targets in Osteoarthritis

“…Resveratrol, examined in previous studies, may prevent the progression of OA through several different mechanisms [166-168]. Interestingly, resveratrol modulates the expression of a number of miRNAs involved in inflammation and disease progressio that including miR-663, miR-155, and miR-2 [169-171].…”

Coenzyme Q10 Prevents the Interleukin‐1 Beta Induced Inflammatory Response via Inhibition of MAPK Signaling Pathways in Rat Articular Chondrocytes

“…Its presence results in attenuation of the potential repair of articular cartilage [Goldring et al, ] by up‐regulating the expression of MMP‐3, MMP‐9, and MMP‐13, which degrade the cartilage matrix [Klatt et al, ]. Inhibition of IL‐1β‐induced MMP and inflammatory mediator production is useful in the treatment of OA [Liu et al, ]. In this study, the production of MMP‐3, MMP‐9, and MMP‐13 was increased in chondrocytes after stimulation by IL‐1β.…”

“…To control the progression of the OA, pharmacological and dietary methods have been used [Kaneva et al, ; Xu et al, ]. Previous studies have showed that natural products might be useful for the treatment of OA and rheumatoid arthritis [Kang et al, ; Liu et al, ; Moon et al, ]. CoQ10, an endogenous antioxidant, can suppress the IL‐1β‐induced inflammatory response in some diseases [Fuller et al, ; Schmelzer et al, ].…”