Dimethyl sulphoxide and dimethyl sulphone are potent inhibitors of IL-6 and IL-8 expression in the human chondrocyte cell line C-28/I2

Kloesch, Burkhard; Liszt, Melissa; Broell, Johann; Steiner, Günter

doi:10.1016/j.lfs.2011.07.015

Cited by 33 publications

(32 citation statements)

References 26 publications

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“…In addition, our current data show that DMA inhibits IL-8 secretion. IL-8 is an important paracrine mediator of inflammation that amplifies inflammatory signals by demargination, activation and chemotaxis of inflammatory cells to the site of injury (64,65). Interestingly, we also demonstrated an increase in intravascular polymorphonuclear (PMN) cells in the murine placenta and uterine tissues in the presence of LPS in vivo, which was significantly reduced by DMA (35).…”

Section: Dma Inhibits the Transcriptional Activity Of Nf-κb But Not Amentioning

confidence: 65%

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N,N-Dimethylacetamide Significantly Attenuates LPS- and TNFα-Induced Proinflammatory Responses Via Inhibition of the Nuclear Factor Kappa B Pathway

Pekson

Poltoratsky

Gorasiya

et al. 2016

Mol Med

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Previously, we have shown that N,N-dimethylacetamide (DMA) prevents inflammation-induced preterm birth in a murine model, inhibits lipopolysaccharide (LPS)-induced increases in placental proinflammatory cytokines and upregulates the antiinflammatory cytokine interleukin-10 (IL-10). However, DMA's mechanism of action remains to be elucidated. In the current study, we investigate how DMA produces its antiinflammatory effect. Using in vitro and ex vivo models, we show that DMA suppresses secretion of proinflammatory cytokines in lipopolysaccharide (LPS)-induced RAW 264.7 cells, TNFα-challenged JEG-3 cells and LPS-stimulated human placental explants. DMA significantly attenuated secretion of TNFα, IL-6, IL-10 and granulocyte macrophage colony stimulating factor (GM-CSF) from LPS-stimulated RAW 264.7 cells; IL-6 secretion from TNFα-stimulated JEG-3 cells; and TNFα, IL-6, IL-10, GM-CSF and Interleukin-8 (IL-8) from LPS-stimulated human placental explants. We further investigated whether DMA's effect on cytokine expression involves the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. DMA (10 mM) significantly inhibited degradation of nuclear factor of kappa light polypeptide gene enhancer in B cell inhibitor α (IκBα) in LPS-stimulated RAW 264.7 cells, but there was no significant change in the expression of phosphorylated or native forms of downstream proteins in the MAPK pathway. In addition, DMA significantly attenuated luciferase activity in cells co-transfected with NF-κB-Luc reporter plasmid, but not with AP-1-Luc or CEBP-Luc reporters. Overall, our findings suggest that the antiinflammatory activity of DMA is mediated by inhibition of the NF-κB pathway via decreased IκBα degradation.

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Section: Dma Inhibits the Transcriptional Activity Of Nf-κb But Not Amentioning

confidence: 65%

“…GM-CSF is an important cytokine produced in the choriodecidua (65). GM-CSF has been reported to be involved in fetal membrane weakening (66) and in regulating the maturation and function of uterine dendritic cells and macrophages as antigen-presenting cells (67).…”

Section: Dma Inhibits the Transcriptional Activity Of Nf-κb But Not Amentioning

confidence: 99%

N,N-Dimethylacetamide Significantly Attenuates LPS- and TNFα-Induced Proinflammatory Responses Via Inhibition of the Nuclear Factor Kappa B Pathway

Pekson

Poltoratsky

Gorasiya

et al. 2016

Mol Med

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“…Dimethylsulfone has been identified as an uremic toxin with optimized metabolomic 1 H NMR approaches [19]. Moreover, the presence of dimethylsulfone likely produced by the gut has been described many years ago for its antioxidant and anti-inflammatory properties, at least in vitro [20, 21, 22]. A decreased urinary concentration of dimethylsulfone in individuals with an altered renal function might be a consequence of a reduced clearance without compensatory tubular secretion.…”

Section: Discussionmentioning

confidence: 99%

Rule-Mining for the Early Prediction of Chronic Kidney Disease Based on Metabolomics and Multi-Source Data

Luck

Bertho

Bateson³

et al. 2016

PLoS ONE

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1H Nuclear Magnetic Resonance (NMR)-based metabolic profiling is very promising for the diagnostic of the stages of chronic kidney disease (CKD). Because of the high dimension of NMR spectra datasets and the complex mixture of metabolites in biological samples, the identification of discriminant biomarkers of a disease is challenging. None of the widely used chemometric methods in NMR metabolomics performs a local exhaustive exploration of the data. We developed a descriptive and easily understandable approach that searches for discriminant local phenomena using an original exhaustive rule-mining algorithm in order to predict two groups of patients: 1) patients having low to mild CKD stages with no renal failure and 2) patients having moderate to established CKD stages with renal failure. Our predictive algorithm explores the m-dimensional variable space to capture the local overdensities of the two groups of patients under the form of easily interpretable rules. Afterwards, a L2-penalized logistic regression on the discriminant rules was used to build predictive models of the CKD stages. We explored a complex multi-source dataset that included the clinical, demographic, clinical chemistry, renal pathology and urine metabolomic data of a cohort of 110 patients. Given this multi-source dataset and the complex nature of metabolomic data, we analyzed 1- and 2-dimensional rules in order to integrate the information carried by the interactions between the variables. The results indicated that our local algorithm is a valuable analytical method for the precise characterization of multivariate CKD stage profiles and as efficient as the classical global model using chi2 variable section with an approximately 70% of good classification level. The resulting predictive models predominantly identify urinary metabolites (such as 3-hydroxyisovalerate, carnitine, citrate, dimethylsulfone, creatinine and N-methylnicotinamide) as relevant variables indicating that CKD significantly affects the urinary metabolome. In addition, the simple knowledge of the concentration of urinary metabolites classifies the CKD stage of the patients correctly.

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“…In vitro studies indicate that the anti-inflammatory activity of this compound is mediated by the inhibition of the proinflammatory nuclear factor kappa beta (NF- κβ ) signaling pathway and attenuation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome activation, resulting in decreased release of the proinflammatory cytokines such as interleukins IL-1 β , IL-6, and IL-8 [6–8]. In addition to pathological conditions, MSM supplementation also alleviates markers of oxidative stress and muscle damage following acute bouts of exercise in a healthy population [9–12].…”

Section: Introductionmentioning

confidence: 99%

The Influence of Methylsulfonylmethane on Inflammation-Associated Cytokine Release before and following Strenuous Exercise

Merwe

2016

Journal of Sports Medicine

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Background. Inflammation is associated with strenuous exercise and methylsulfonylmethane (MSM) has been shown to have anti-inflammatory properties. Methods. Physically active men were supplemented with either placebo or MSM (3 grams per day) for 28 days before performing 100 repetitions of eccentric knee extension exercise. Ex vivo and in vitro testing consisted of evaluating cytokine production in blood (whole blood and isolated peripheral blood mononuclear cells (PBMCs)) exposed to lipopolysaccharide (LPS), before and through 72 hours after exercise, while in vivo testing included the evaluation of cytokines before and through 72 hours after exercise. Results. LPS stimulation of whole blood after MSM supplementation resulted in decreased induction of IL-1β, with no effect on IL-6, TNF-α, or IL-8. After exercise, there was a reduced response to LPS in the placebo, but MSM resulted in robust release of IL-6 and TNF-α. A small decrease in resting levels of proinflammatory cytokines was noted with MSM, while an acute postexercise increase in IL-10 was observed with MSM. Conclusion. Strenuous exercise causes a robust inflammatory reaction that precludes the cells from efficiently responding to additional stimuli. MSM appears to dampen the release of inflammatory molecules in response to exercise, resulting in a less incendiary environment, allowing cells to still have the capacity to mount an appropriate response to an additional stimulus after exercise.

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Dimethyl sulphoxide and dimethyl sulphone are potent inhibitors of IL-6 and IL-8 expression in the human chondrocyte cell line C-28/I2

Cited by 33 publications

References 26 publications

N,N-Dimethylacetamide Significantly Attenuates LPS- and TNFα-Induced Proinflammatory Responses Via Inhibition of the Nuclear Factor Kappa B Pathway

N,N-Dimethylacetamide Significantly Attenuates LPS- and TNFα-Induced Proinflammatory Responses Via Inhibition of the Nuclear Factor Kappa B Pathway

Rule-Mining for the Early Prediction of Chronic Kidney Disease Based on Metabolomics and Multi-Source Data

The Influence of Methylsulfonylmethane on Inflammation-Associated Cytokine Release before and following Strenuous Exercise

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