Interleukin-1β and interleukin-6 disturb the antioxidant enzyme system in bovine chondrocytes: a possible explanation for oxidative stress generation

Sylvester

The Journal of Immunology

et al. 2009

Aggrecanases (a dystrophin and metalloproteinase with thrombospondin motif, ADAMTSs) are principal proteases involved in cartilage extracellular matrix aggrecan degradation. The role and relative contribution of MyD88, IRAK1, and TRAF6 adaptor proteins in IL-1β regulation of aggrecanase-1 (ADAMTS-4) is unknown. By small interfering RNAs-mediated knockdown, we show that IL-1β-induced up-regulation of ADAMTS-4 in chondrocytes requires MyD88, IRAK1, and TRAF6 adaptor proteins. However, partial inhibition of ADAMTS-4 induction by their knockdown suggested the involvement of additional signaling proteins. Because IL-1β is also known to induce reactive oxygen species (ROS) through Ras-mediated activation of NADPH oxidase, we investigated the implication of Ras in ADAMTS-4 regulation. Ras knockdown, or inhibition of ROS by antioxidants along with the ablation of MyD88, IRAK1, or TRAF6 more potently down-regulated IL-1β-induced ADAMTS-4. In addition, IL-1β-induced phosphorylation of downstream effectors, IκB kinase αβ, IκBα, and activation of transcription factor NF-κB was significantly reduced in the MyD88-, IRAK1-, TRAF6-, or Ras-deficient cells. The combined knockdown of Ras and individual adaptor proteins strongly blocked the activation of IKKαβ, IκBα, and NF-κB. These findings suggest that Ras, ROS along with MyD88, IRAK1, or TRAF6 synergistically mediate ADAMTS-4 regulation by IL1-β. Thus, complete ablation of ADAMTS-4 induction could be achieved by combined inhibition of Ras and individual adaptor proteins, which may be of therapeutic value in arthritis.

Section: Discussionmentioning

confidence: 87%

Adaptor Proteins and Ras Synergistically Regulate IL-1-Induced ADAMTS-4 Expression in Human Chondrocytes

Sylvester

The Journal of Immunology

et al. 2009

“…H 2 O 2 can cause oxidative stress when H 2 O 2 detoxification enzymes are ineffective or depleted. CAT and GPX are the principal H 2 O 2 detoxifying enzymes (Mathy-Hartert et al 2008). Following exposure of cells to 1 ng/ mL IL-1b, the highest GSH-Px level was observed for the 50 lg/ mL concentrated ethyl acetate extract of P. endlicherianum.…”

Section: Discussionmentioning

confidence: 97%

Chemical composition and biological investigation of Pelargonium endlicherianum root extracts

Karatoprak

Göğer

Yerer

et al. 2017

Pharmaceutical Biology

Context: Pelargonium endlicherianum Fenzl. (Geraniaceae) roots and flowers are traditionally used in Turkey as a decoction treatment against intestinal parasites. Neither the chemical composition nor the potential bioactivity of the plant roots has been studied before. Objectives: The phenolic content and effects of P. endlicherianum root extracts on antioxidant enzyme levels on A549 cells were studied for the first time. Materials and methods: The chemical composition was analyzed via spectrophotometric and chromatographic (HPLC MS/MS and HPLC) techniques. The antioxidant activity was determined at different concentrations ranging from 0.001 to 2 mg/mL using DPPH and ABTS þ radical scavenging activity, b-carotenelinoleic acid co-oxidation assay, protection of 2-deoxyribose and bovine brain-derived phospholipids against a hydroxyl radical-mediated degradation assay. Glutathione peroxidase and superoxide dismutase activities were also studied as well as the effects of the extracts on nitric oxide levels on IL-1b stimulated A549 cells. Results: The key parameters for the most active ethyl acetate extract included the following: DPPH IC 50 : 0.23 mg/mL, TEAC/ABTS: 2.17 mmol/L Trolox, reduction: 0.41 mmol/g AsscE, and protection of lipid peroxidation IC 50 : 0.05 mg/mL. Furthermore, the ethyl acetate extract increased the SOD level significantly compared to control group (4.48 U/mL) at concentrations of 100 and 200 lg/mL SOD, 5.50 and 5.67 U/mL, respectively. Apocynin was identified as the major component, and the ethyl acetate fraction was found to be rich in phenolic compounds. Discussion and conclusion: Pelargonium endlicherianum root extracts displayed antioxidant activity and increased the antioxidant enzyme levels in IL-1b stimulated A549 cells, while decreasing the NO levels.ARTICLE HISTORY

“…As previously mentioned articular cartilage is an avascular tissue where its nutrients come from synovial fluid and the oxygen tension is only about 1-7% (52,53).…”

Section: Role Of Oxidative Stress In Oamentioning

confidence: 99%

Modulation of inflammation and oxidative stress in canine chondrocytes

Dycus

Grzanna

et al. 2013

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