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Resveratrol inhibits TNF-α-induced IL-1β, MMP-3 production in human rheumatoid arthritis fibroblast-like synoviocytes via modulation of PI3kinase/Akt pathway

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Abstract

Resveratrol (trans-3,4′-trihydroxystilbene), a natural phytoalexin, possesses anti-inflammatory, anti-proliferative, and immunomodulatory properties and has the potential for treating inflammatory disorders. The present study was designed to investigate the effects of resveratrol on TNF-α-induced inflammatory cytokines production of IL-1β and MMP3 in Rheumatoid arthritis (RA) Fibroblast-like synoviocytes (FLS) and further to explore the role of PI3K/Akt signaling pathway by which resveratrol modulates those cytokines production. The levels of IL-1β, MMP-3 in cultural supernatants among groups were measured by enzyme-linked immunosorbent assay. Messenger RNA expression of IL-1β and MMP-3 in RA FLS was analyzed using a reverse transcription-polymerase chain reaction. Western blot analysis was used to detect proteins expression in RA FLS intervened by resveratrol. Resveratrol inhibited both mRNA and proteins expressions of IL-1β and MMP-3 on RA FLS in a dose-dependent manner. Resveratrol also decreased significantly the expression of phosphorylated Akt dose dependently. Activation of PI3K/Akt signaling pathway exists in TNF-α-induced production of IL-1β and MMP3 on RA FLS, which is hampered by PI3K inhibitor LY294002. Immunofluorescence staining showed that TNF-α alone increased the production of P-Akt, whereas LY294002 and 50 μM resveratrol suppressed the TNF-α-stimulated expression of P-Akt. Resveratrol attenuates TNF-α-induced production of IL-1β and MMP-3 via inhibition of PI3K-Akt signaling pathway in RA FLS, suggesting that resveratrol plays an anti-inflammatory role and might have beneficial effects in preventing and treating RA.

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Acknowledgments

This study was supported in part by a grant for Administration of Traditional Chinese medicine of Hunan Province, China (No. 2009065).

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Authors and Affiliations

  1. Department of Rheumatology and Immunology, Xiang Ya Second Hospital, Central South University, Changsha, 410011, China

    Jing Tian, Jin-wei Chen, Jie-sheng Gao, Len Li & Xi Xie

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  1. Jing Tian
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  2. Jin-wei Chen
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  3. Jie-sheng Gao
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  4. Len Li
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  5. Xi Xie
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Correspondence to Jin-wei Chen.

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Tian, J., Chen, Jw., Gao, Js. et al. Resveratrol inhibits TNF-α-induced IL-1β, MMP-3 production in human rheumatoid arthritis fibroblast-like synoviocytes via modulation of PI3kinase/Akt pathway. Rheumatol Int 33, 1829–1835 (2013). https://doi.org/10.1007/s00296-012-2657-0

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  • DOI: https://doi.org/10.1007/s00296-012-2657-0

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