Delphinidin Inhibits Il-1 Beta-induced Activation Of Nf-kappa B By Modulating The Phosphorylation Of Irak-1(ser376) In Human Articular Chondrocytes
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
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.
Haseeb A; Chen D X; Haqqi T M
Rheumatology
2013
2013-06
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1093/rheumatology/kes363" target="_blank" rel="noreferrer noopener">10.1093/rheumatology/kes363</a>
Response of engineered cartilage tissue to biochemical agents as studied by proton magnetic resonance microscopy
acid; anterior cruciate ligament; canine articular-cartilage; chondrocytes; interleukin-1; matrix; nmr; osteoarthritis; Rheumatology; self-diffusion; water
Objective, To test the hypothesis that magnetic resonance imaging (MRI) results correlate with the biochemical composition of cartilage matrix and can therefore be used to evaluate natural tissue development and the effects of biologic interventions. Methods. Chondrocytes harvested from day-16 chick embryo sterna were inoculated into an MRI-compatible hollow-fiber bioreactor, The tissue that formed over a period of 2-4 weeks was studied biochemically, histologically, and with MRI. Besides natural development, the response of the tissue to administration of retinoic acid, interleukin-1 beta (IL-1 beta), and daily dosing with ascorbic acid was studied. Results. Tissue wet and dry weight, glycosaminoglycan (GAG) content, and collagen content all increased with development time, while tissue hydration decreased. The administration of retinoic acid resulted in a significant reduction in tissue wet weight, proteoglycan content, and cell number and an increase in hydration as compared with controls. Daily dosing with ascorbic acid increased tissue collagen content significantly compared with controls, while the administration of IL-1 beta resulted in increased proteoglycan content. The water proton longitudinal and transverse relaxation rates correlated well with GAG and collagen concentrations of the matrix as well as with tissue hydration. In contrast, the magnetization transfer value for the tissue correlated only with total collagen, Finally, the self-coefficient of water correlated with tissue diffusion hydration. Conclusion. Parameters derived from MR images obtained noninvasively can be used to quantitatively assess the composition of cartilage tissue generated in a bioreactor. We conclude that MRI is a promising modality for the assessment of certain biochemical properties of cartilage in a wide variety of settings.
Potter K; Butler J J; Horton W E; Spencer R G S
Arthritis and Rheumatism
2000
2000-07
Journal Article
<a href="http://doi.org/10.1002/1529-0131(200007)43:7%3C1580::aid-anr23%3E3.3.co;2-7" target="_blank" rel="noreferrer noopener">10.1002/1529-0131(200007)43:7%3C1580::aid-anr23%3E3.3.co;2-7</a>