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[RETRACTED ARTICLE] Ginsenoside Rd inhibits IL-1β-induced inflammation and degradation of intervertebral disc chondrocytes by increasing IL1RAP ubiquitination

Abstract

Many compounds of ginsenosides show anti-inflammatory properties. However, their anti-inflammatory effects in intervertebral chondrocytes in the presence of inflammatory factors have never been shown. Increased levels of pro-inflammatory cytokines are generally associated with the degradation and death of chondrocytes; therefore, finding an effective and nontoxic substance that attenuates the inflammation is worthwhile. In this study, chondrocytes were isolated from the nucleus pulposus tissues, and the cells were treated with ginsenoside compounds and IL-1β, alone and in combination. Cell viability and death rate were assessed by CCK-8 and flow cytometry methods, respectively. PCR, western blot, and immunoprecipitation assays were performed to determine the mRNA and protein expression, and the interactions between proteins, respectively. Monomeric component of ginsenoside Rd had no toxicity at the tested range of concentrations. Furthermore, Rd suppressed the inflammatory response of chondrocytes to interleukin (IL)-1β by suppressing the increase in IL-1β, tumor necrosis factor (TNF)-α, IL-6, COX-2, and inducible nitric oxide synthase (iNOS) expression, and retarding IL-1β-induced degradation of chondrocytes by improving cell proliferation characteristics and expression of aggrecan and COL2A1. These protective effects of Rd were associated with ubiquitination of IL-1 receptor accessory protein (IL1RAP), blocking the stimulation of IL-1β to NF-κB. Bioinformatics analysis showed that NEDD4, CBL, CBLB, CBLC, and ITCH most likely target IL1RAP. Rd increased intracellular ITCH level and the amount of ITCH attaching to IL1RAP. Thus, IL1RAP ubiquitination promoted by Rd is likely to occur by up-regulation of ITCH. In summary, Rd inhibited IL-1β-induced inflammation and degradation of intervertebral disc chondrocytes by increasing IL1RAP ubiquitination.

Ginsenoside Rd; IL-1β; Inflammation; Degradation; Intervertebral disc chondrocytes; IL1RAP ubiquitination


Retraction for: Braz J Med Biol Res | doi: http://10.1590/1414-431x20198525 | PMCID: PMC6694592 | PMID: 31411316

The authors would like to retract the article “Ginsenoside Rd inhibits IL-1β-induced inflammation and degradation of intervertebral disc chondrocytes by increasing IL1RAP ubiquitination” that was published in volume 52 no. 9 (2019) (Epub Aug 12, 2019) in the Brazilian Journal of Medical and Biological Research <http://dx.doi.org/10.1590/1414-431x20198525> PMCID: PMC6694592 | PMID: 31411316.

The Corresponding author Ya-Li Wu states that “there is a conflict between authors concerning the publication of Figure 1 Aa and Ab, which had already been published in a Chinese Journal”. Therefore, this article is being retracted and all authors will be prohibited to publish in the Brazilian Journal of Medical and Biological Research in the future.

Publication Dates

  • Publication in this collection
    12 Aug 2019
  • Date of issue
    2019

History

  • Received
    22 Jan 2019
  • Accepted
    29 May 2019
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