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Báo cáo y học: "A peptidyl-glucosamine derivative affects IKKa kinase activity in human chondrocytes"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài: A peptidyl-glucosamine derivative affects IKKa kinase activity in human chondrocytes. | Scotto d Abusco et al. Arthritis Research Therapy 2010 12 R18 http arthritis-research.eom content 12 1 R18 RESEARCH ARTICLE Open Access A peptidyl-glucosamine derivative affects IKKa kinase activity in human chondrocytes Anna Scotto d Abusco1 Laura Politi1 Cesare Giordano2 Roberto Scandurra1 Abstract Introduction Nuclear factor-KB NF-kB transcription factor regulates several cell signaling pathways such as differentiation and inflammation which are both altered in osteoarthritis. Inhibitor kB kinase IKK a and IKKp are kinases involved in the activation of the NF-kB transcription factor. The aim of the present study was to determine the effects of glucosamine GlcN which is administered in the treatment of osteoarthritis and of its 2- N-Acetyl -L-phenylalanylamido-2-deoxy-p-D-glucose NAPA derivative on IKK kinases and consequently on NF-kB activation in human chondrocytes. Methods The human chondrosarcoma cell line HTB-94 and human primary chondrocytes were stimulated with tumor necrosis factor TNF a after pre-treatment with GlcN or NAPA. Gene mRNA expression level was evaluated by real-time PCR. Inhibitor kB protein I B a phosphorylation and p65 nuclear re-localization were analyzed by Western blotting IKKa nuclear re-localization was also investigated by immunocytochemistry and Western blotting. IKK kinase activity was studied by in vitro kinase assay. Results After TNFa stimulation the mRNA expression level of some of the genes under NF-kB control such as interleukin IL -6 and IL-8 increased while treatment with GlcN and NAPA reverted the effect. We investigated the possibility that GlcN and NAPA inhibit IKK kinase activity and found that NAPA inhibits the IKKa kinase activity whereas GlcN does not. Interestingly both GlcN and NAPA inhibit IKKa nuclear re-localization. Conclusions Our results demonstrate that glucosamine and its peptidyl derivative can interfere with NF-kB signaling pathway by inhibiting IKKa activity in human chondrocytes. However the mechanism .