title: Delphinidin inhibits IL-1β-induced activation of NF-κB by modulating the phosphorylation of IRAK-1(Ser376) in human articular chondrocytes.
abstract: OBJECTIVE
  In OA, there is enhanced expression of pro-inflammatory cytokines such as IL-1β in the affected joint. Delphinidin, an anthocyanidin found in pigmented fruits and vegetables, has been shown to possess anti-inflammatory and antioxidant properties. In the present study we determined whether delphinidin would inhibit the IL-1β-induced activation of NF-κB in human chondrocytes and determined the mechanism of its action.
  
  
  METHODS
  PGE2 levels and activation of NF-κB p65 in human OA chondrocytes were determined by ELISA-based assays. Protein expression of cyclo-oxygenase-2 (COX-2) and phosphorylation of kinases was determined by western immunoblotting. Expression level of mRNAs was determined by TaqMan assays.
  
  
  RESULTS
  Delphinidin inhibited IL-1β-induced expression of COX-2 and production of PGE2 in human chondrocytes. Delphinidin also inhibited IL-1β-mediated phosphorylation of IL-1 receptor-associated kinase-1(Ser376), phosphorylation of IKKα/β, expression of IKKβ, degradation of IκBα, and activation and nuclear translocation of NF-κB/p65. Phosphorylation of TGF-β-activated kinase 1 was not observed but NF-κB-inducing kinase (NIK) was phosphorylated and phosphorylation of NIK was blocked by delphinidin in IL-1β-treated human chondrocytes.
  
  
  CONCLUSIONS
  These data identify delphinidin as a novel inhibitor of IL-1β-induced production of cartilage-degrading molecule PGE2 via inhibition of COX-2 expression and provide new insight into the mechanism of its action. Our results also identify inhibition of IRAK1(Ser376) phosphorylation by delphinidin in IL-1β-induced activation of NF-κB in human chondrocytes. Given the important role played by IL-1β-induced NF-κB activation, COX-2 expression and PGE2 production in OA, our results may have important implications for the development of novel therapeutic strategies for the prevention/treatment of OA.
authors: Department of Medicine, Division of Rheumatology, MetroHealth Medical Centre/Case Western Reserve University, Cleveland, OH, USA.
authors: Abdul
authors: A
authors: Haseeb
authors: Dongxing
authors: D
authors: Chen
authors: Tariq M
authors: TM
authors: Haqqi
mesh_terms: D000872:Anthocyanins / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism*; D053583:Interleukin-1beta / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013450:Sulfones / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D000872:Anthocyanins; D053583:Interleukin-1beta; D016328:NF-kappa B; D009570:Nitriles; D017472:Receptors, Interleukin-1; D013450:Sulfones; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases; C017185:delphinidin; D015232:Dinoprostone
keywords: COX-2; IL-1β; NF-κB; PGE2; chondrocytes; delphinidin; osteoarthritis
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