Delphinidin Inhibits Il-1 Beta-induced Activation Of Nf-kappa B By Modulating The Phosphorylation Of Irak-1(ser376) In Human Articular Chondrocytes

Delphinidin Inhibits Il-1 Beta-induced Activation Of Nf-kappa B By Modulating The Phosphorylation Of Irak-1(ser376) In Human Articular Chondrocytes

Haseeb A; Chen D X; Haqqi T M

Rheumatology

2013

2013-06

Objective. In OA, there is enhanced expression of pro-inflammatory cytokines such as IL-1 beta 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-1 beta-induced activation of NF-kappa B in human chondrocytes and determined the mechanism of its action. Methods. PGE(2) levels and activation of NF-kappa B 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-1 beta-induced expression of COX-2 and production of PGE(2) in human chondrocytes. Delphinidin also inhibited IL-1 beta-mediated phosphorylation of IL-1 receptor-associated kinase-1(Ser376), phosphorylation of IKK alpha/beta, expression of IKK beta, degradation of I kappa B alpha, and activation and nuclear translocation of NF-kappa B/p65. Phosphorylation of TGF-beta-activated kinase 1 was not observed but NF-kappa B-inducing kinase (NIK) was phosphorylated and phosphorylation of NIK was blocked by delphinidin in IL-1 beta-treated human chondrocytes. Conclusion. These data identify delphinidin as a novel inhibitor of IL-1 beta-induced production of cartilage-degrading molecule PGE(2) 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-1 beta-induced activation of NF-kappa B in human chondrocytes. Given the important role played by IL-1 beta-induced NF-kappa B activation, COX-2 expression and PGE(2) production in OA, our results may have important implications for the development of novel therapeutic strategies for the prevention/treatment of OA.

chondrocytes; COX-2; delphinidin; down-regulation; factor-alpha; gene-expression; human osteoarthritis chondrocytes; IL-1 beta; in-vitro; interleukin-1; kinase; nf-kappa-b; osteoarthritis; oxidative stress; PGE(2); rheumatoid-arthritis; Rheumatology; tumor-necrosis-factor

Journal Article or Conference Abstract Publication

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998-1008

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