Resveratrol inhibits the IL-1β-induced expression of MMP-13 and IL-6 in human articular chondrocytes via TLR4/MyD88-dependent and -independent signaling cascades

Gu, Hailun; Jiao, Yongliang; Yu, Xiaolu; Li, Xingyao; Wang, Wei; Ding, Lifeng; Liu, Li

doi:10.3892/ijmm.2017.2885

Cited by 45 publications

(30 citation statements)

References 40 publications

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“…Besides, while IL-1β stimulation increased the upregulation of TLR4 and downstream targets in both dependent and independent TLR4/MyD88 signaling pathways, co-treatment with resveratrol suppressed both catabolic and inflammatory responses in a dose-dependent manner. Resveratrol reduced the expression levels of MMP-13, IL-6, TNF-α, phospho-interleukin-1 receptor-associated kinase 4 (p-IRAK4), and TLR4-tumor necrosis factor receptor-associated factor 6 (TRAF6) mediators of the TLR4/MyD88 signaling pathways [113]. Similar results were observed in obesity-related OA in an animal model.…”

Section: Resveratrolsupporting

confidence: 64%

Unraveling Natural Products’ Role in Osteoarthritis Management—An Overview

et al. 2020

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The natural process of aging gradually causes changes in living organisms, leading to the deterioration of organs, tissues, and cells. In the case of osteoarthritis (OA), the degradation of cartilage is a result of both mechanical stress and biochemical factors. Natural products have already been evaluated for their potential role in the prevention and treatment of OA, providing a safe and effective adjunctive therapeutic approach. This review aimed to assess the therapeutic potential of natural products and their derivatives in osteoarthritis via a systematic search of literature after 2008, including in vitro, in vivo, ex vivo, and animal models, along with clinical trials and meta-analysis. Overall, 170 papers were obtained and screened. Here, we presented findings referring to the preventative and therapeutic potential of 17 natural products and 14 naturally occurring compounds, underlining, when available, the mechanisms implicated. The nature of OA calls to initially focus on the management of symptoms, and, in that context, several naturally occurring compounds have been utilized. Underlying a global need for more sustainable natural sources for treatment, the evidence supporting their chondroprotective potential is still building up. However, arriving at that kind of solution requires more clinical research, targeting the implications of long-term treatment, adverse effects, and epigenetic implications.

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Section: Resveratrolsupporting

confidence: 64%

Unraveling Natural Products’ Role in Osteoarthritis Management—An Overview

et al. 2020

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“…Therefore, research efforts have focused on the development of several natural and synthetic agents in order to attenuate inflammation at the molecular level. Resveratrol inhibits the IL-1β-induced expression of matrix metalloproteinase-13, IL-6 and TNF-α via the TLR4/MyD88-dependent signaling cascades ( 23 , 24 ), and it further attenuates neuronal autophagy and inflammatory injury in experimental traumatic brain injury ( 25 ). Diallyl trisulfide exerts anti-inflammatory effects via suppressing the TLR4/NF-κB signaling pathway in lipopolysaccharide (LPS)-stimulated Raw 264.7 macrophages and isch-emic stroke-induced inflammation ( 26 , 27 ).…”

Section: Introductionmentioning

confidence: 99%

DFMG attenuates the activation of macrophages induced by co‑culture with LPC‑injured HUVE‑12 cells via the TLR4/MyD88/NF‑κB signaling pathway

Yang

Zhang

et al. 2018

Int J Mol Med

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7-difluoromethoxy-5,4′-dimethoxy-genistein (DFMG) is a novel active chemical entity, which modulates the function and signal transduction of endothelial cells and macrophages (MPs), and is essential in the prevention of atherosclerosis. In the present study, the activity and molecular mechanism of DFMG on MPs was investigated using a Transwell assay to construct a non-contact co-culture model. Human umbilical vein endothelial cells (HUVE-12), which were incubated with lysophosphatidylcholine (LPC), were seeded in the upper chambers, whereas PMA-induced MPs were grown in the lower chambers. The generation of reactive oxygen species (ROS) and the release of lactate dehydrogenase (LDH) were measured using the corresponding assay kits. The proliferation and migration were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and wound healing assays, respectively. Foam cell formation was examined using oil red O staining and a total cholesterol assay. The protein expression levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factor (NF)-κB p65 were detected by western immunoblotting. The secretion of interleukin (IL)-1β was examined using an enzyme-linked immunosorbent assay. It was found that LPC significantly increased the generation of ROS and the release of LDH in HUVE-12 cells. The LPC-injured HUVE-12 cells activated MPs under co-culture conditions and this process was inhibited by DFMG treatment. LPC upregulated the expression levels of TLR4, MyD88 and NF-κB p65, and the secretion of IL-1β in the supernatant of the co-cultured HUVE-12 cells and MPs. These effects were reversed by the application of DFMG. Furthermore, CLI-095 and IL-1Ra suppressed the activation of MPs that was induced by co-culture with injured HUVE-12 cells. These effects were further enhanced by co-treatment with DFMG, and DFMG exhibited synergistic effects with a TLR4-specific inhibitor. Take together, these findings revealed that DFMG attenuated the activation of MP induced by co-culture with LPC-injured HUVE-12 cells. This process was mediated via inhibition of the TLR4/MyD88/NF-κB signaling pathway in HUVE-12 cells.

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“…After stimulated with IL-1β, MMPs were significantly upregulated [ 26 ]. Gu et al [ 27 ] presented that RSV suppresses the expression of IL-6 and MMP-13 in IL-1β-induced human articular chondrocytes via signaling cascades that are independent and dependent of TLR4/MyD88. As a result, we hypothesized that RSV reduces MMP production and activation during the progression of OA, then exerting an anti-inflammatory influence.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol alleviates the interleukin-1β-induced chondrocytes injury through the NF-κB signaling pathway

Zhang

Cui

et al. 2020

J Orthop Surg Res

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Background Osteoarthritis (OA) is a regular age-related disease that affects millions of people. Resveratrol (RSV) is a flavonoid with a stilbene structure with different pharmacological effects. The purpose of the experiment was to evaluate the protective role of RSV against the human OA chondrocyte injury induced by interleukin-1β (IL-1β). Methods Chondrocytes were isolated from OA patients and identified by type II collagen, safranin O staining, and toluidine blue staining. Differentially expressed genes in chondrocytes treated RSV were identified by RNA sequencing. Kyoto encyclopedia of genes and genomes (KEGG) pathway as well as gene ontology (GO) were further conducted through Metascape online tool. A cell counting kit-8 (CCK-8) assay was applied to discover the viability of chondrocytes (6, 12, 24, and 48 μM). Many genes associated with inflammation and matrix degradation are evaluated by real-time PCR (RT-PCR) as well as western blot (WB). The mechanism of RSV for protecting IL-1β induced chondrocytes injury was further measured through immunofluorescence and WB assays. Results A total of 845 differentially expressed genes (upregulated = 499, downregulated = 346) were found. These differentially expressed genes mainly enriched into negative regulation of catabolic process, autophagy, and cellular catabolic process, intrinsic apoptotic, apoptotic, and regulation of apoptotic signaling pathway, cellular response to abiotic stimulus, external stimuli, stress, and radiation. These differentially expressed genes were obviously enriched in NF-kB signaling pathway. RSV at the concentration of 48 μM markedly weakened the viability of the cells after 24 h of treatment (87% vs 100%, P < 0.05). No obvious difference was observed between the 6, 12, and 24 μM groups (106% vs 100%, 104% vs 100%, 103% vs 100%, P > 0.05). RSV (24 μM) also markedly depressed the levels of PGE2 and NO induced by IL-1β by 25% and 29% respectively (P < 0.05). Our experiment pointed out that RSV could dramatically inhibit the inflammatory response induced by IL-1β, including the MMP-13, MMP-3, and MMP-1 in human OA chondrocytes by 50%, 35%, and 33% respectively. On the other hand, RSV inhibited cyclooxygenase-2 (COX-2), matrix metalloproteinase-1 (MMP-1), MMP-3, MMP-13, and inducible nitric oxide synthase (iNOs) expression (P < 0.05), while increased collagen-II and aggrecan levels (P < 0.05). From a mechanistic perspective, RSV inhibited the degradation of IκB-α as well as the activation of nuclear factor-kappa B (NF-κB) induced by IL-1β. Conclusion In summary, RSV regulates the signaling pathway of NF-κB, thus inhibiting inflammation and matrix degradation in chondrocytes. More studies should be focused on the treatment efficacy of RSV for OA in vivo.

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Resveratrol inhibits the IL-1β-induced expression of MMP-13 and IL-6 in human articular chondrocytes via TLR4/MyD88-dependent and -independent signaling cascades

Cited by 45 publications

References 40 publications

Unraveling Natural Products’ Role in Osteoarthritis Management—An Overview

Unraveling Natural Products’ Role in Osteoarthritis Management—An Overview

DFMG attenuates the activation of macrophages induced by co‑culture with LPC‑injured HUVE‑12 cells via the TLR4/MyD88/NF‑κB signaling pathway

Resveratrol alleviates the interleukin-1β-induced chondrocytes injury through the NF-κB signaling pathway

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