Abstract
Introduction
There have been several cases reporting a significant increase in chondroitin sulphate plasma levels in patients with different types of disease, such as systemic lupus erythematosus, rheumatoid arthritis, and liver disease. At present, the precise role of chondroitin sulphate molecules in blood is unclear. Previous investigations have shown that the addition of purified human plasma glycosaminoglycans (GAGs), containing a high percentage of chondroitin-4-sulphate (C4S) was able to inhibit lipid peroxidation and to protect cells from reactive oxygen species damage, suggesting antioxidant activity. Starting from these reports, the aim of this study was to evaluate the effectiveness of GAG structures purified from normal human plasma in reducing inflammation using a model of lipopolysaccharide (LPS)-induced increase of pro-inflammatory cytokines in mouse articular chondrocyte cultures.
Results
Chondrocyte stimulation with LPS (50 μg/ml) for 24 h enhanced gene expression of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin 6 (IL-6), interferon gamma (IFN-γ), inducible nitric oxide synthase (iNOS) and increases in their related protein levels, as well as NF-κB activation, IκBα phosphorylation and apoptosis evaluated by the increase in caspase-3 expression and its related protein amount. LPS treatment also generated a high amount of nitric oxide (NO). The addition of different doses of purified human GAGs to LPSstimulated chondrocytes reduced inflammatory cytokines and iNOS both at mRNA and protein levels, blocked NF-κB activation and cytoplasmic IκBα phosphorylation, limited cell death by inhibiting apoptosis, and reduced NO concentrations.
Conclusions
These results further support the hypothesis that plasma GAGs may function as immunomodulators and their increased release and degradation could be a biological response acting to modulate inflammation during disease.
At the request of the journal Editor and Sage the following article has been retracted:
Campo GM, Avenoso A, Campo S, et al. Purified human plasma glycosaminoglycans reduced NF-κB activation, pro-inflammatory cytokine production and apoptosis in LPS-treated chondrocytes. Innate Immunity. 2008;14(4):233–246. doi:10.1177/1753425908094725
Sage was alerted to a discussion surrounding the article on PubPeer.
Following an internal investigation, several concerns have been raised about multiple images in the article:
1. Figure 1 appears to contain duplication across images CTRL and CTRL + P-GAG 2.0 mg/ml; LPS + P-GAG 0.5 mg/ml and LPS + P-GAG 1.0 mg/ml; LPS and LPS + P-GAG 2.0 mg/ml
2. Figures 2B, 3B, 4B, 5B and 6B appear to have overlapping features across figures and lanes.
3. Figures 2B, 3B, 4B have background irregularities that could indicate potential background correction, and appear to have duplicate bands across figures.
4. Figure 5B: potential splicing between lanes 2 and 3, 5 and 6.
5. Figure 6B: potential splicing between lanes 2 and 3, 3 and 4, 4 and 5, 5 and 6.
6. Figure 7B: potential splicing between lanes 3 and 4, 4 and 5, 5 and 6.
The authors provided some images representing findings underlying these figure panels, and some data underlying the graphs. Sage and the Journal Editor assessed these materials and determined that they do not resolve the concerns raised.
Due to the nature of the original concern, lack of appropriate raw images or data to resolve the concerns raised, the Journal Editor believes there are outstanding questions about the validity of the findings and retracts this article.
The authors did not agree with the retraction.