A peptidyl-glucosamine derivative affects IKK[alpha] kinase activity in human chondrocytes

Introduction Nuclear factor-[kappa]B (NF-[kappa]B) transcription factor regulates several cell signaling pathways, such as differentiation and inflammation, which are both altered in osteoarthritis. Inhibitor [kappa]B kinase (IKK)[alpha] and IKK[beta] are kinases involved in the activation of the NF...

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Bibliographic Details
Published in:Arthritis research & therapy 2010-01, Vol.12, p.R18
Main Authors: Scotto d'Abusco, Anna, Politi, Laura, Giordano, Cesare, Scandurra, Roberto
Format: Article
Language:English
Subjects:
Care and treatment
Cartilage cells
Cellular signal transduction
Genetic aspects
Glucosamine
Health aspects
Osteoarthritis
Patient outcomes
Physiological aspects
Transcription factors
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Summary:Introduction Nuclear factor-[kappa]B (NF-[kappa]B) transcription factor regulates several cell signaling pathways, such as differentiation and inflammation, which are both altered in osteoarthritis. Inhibitor [kappa]B kinase (IKK)[alpha] and IKK[beta] are kinases involved in the activation of the NF-[kappa]B 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-[beta]-D-glucose (NAPA) derivative on IKK kinases and, consequently, on NF-[kappa]B activation in human chondrocytes. Methods The human chondrosarcoma cell line HTB-94 and human primary chondrocytes were stimulated with tumor necrosis factor (TNF)[alpha] after pre-treatment with GlcN or NAPA. Gene mRNA expression level was evaluated by real-time PCR. Inhibitor [kappa]B protein (I[kappa]B)[alpha] phosphorylation and p65 nuclear re-localization were analyzed by Western blotting; IKK[alpha] nuclear re-localization was also investigated by immunocytochemistry and Western blotting. IKK kinase activity was studied by in vitro kinase assay. Results After TNF[alpha] stimulation, the mRNA expression level of some of the genes under NF-[kappa]B 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 IKK[alpha] kinase activity, whereas GlcN does not. Interestingly, both GlcN and NAPA inhibit IKK[alpha] nuclear re-localization. Conclusions Our results demonstrate that glucosamine and its peptidyl derivative can interfere with NF-[kappa]B signaling pathway by inhibiting IKK[alpha] activity in human chondrocytes. However, the mechanism of action of the two molecules is not completely overlapping. While NAPA can both specifically inhibit the IKK[alpha] kinase activity and IKK[alpha] nuclear re-localization, GlcN only acts on IKK[alpha] nuclear re-localization.
ISSN:1478-6354
DOI:10.1186/ar2920