The Catabolic Role of Toll-Like Receptor 2 (TLR-2) Mediated by the NF-kappa B Pathway in Septic Arthritis
AuthorPapathanasiou, I.; Malizos, K. N.; Poultsides, L.; Karachalios, T.; Oikonomou, P.; Tsezou, A.
Toll-like receptors (TLRs) are involved in mediating cell activation on stimulation with microbial components. Our objective was to investigate the role of 'PLR-2 mediated by the NF-kappa B pathway in septic arthritic chondrocytes. TLR-1, -2, and -6 mRNA expression levels were investigated in septic and normal chondrocytes using real-time reverse transcription-PCR. TLR-2 and MMP-13 mRNA and protein levels were measured using real-time PCR and Western blot analysis, respectively. Blocking TLR-2 mRNA expression was performed using small interfering-RNA (siRNA) against TLR-2 and subsequently MMP-3, MMP-13,1L-1 beta, and IL-6 mRNA levels, as well as p65 NF-kappa B, IkB alpha, and MMP-13 protein levels were evaluated using real-time PCR and Western blot analysis. IL-6 protein levels were measured using ELISA assay. We observed that TLR-1, -2, and -6 mRNA expression levels were significantly higher in septic compared to normal chondrocytes. MMP-13 mRNA and protein expressions were also significantly upregulated in septic arthritic cartilage. Blocking TLR-2 mRNA expression in septic chondrocytes resulted in significant increase of inactivated nonphosphorylatecl p65 NF-kappa B and IkB alpha protein levels and reduction in MMP-13, IL-1 beta, and IL-6 expression. Our findings suggest the pro-inflammatory and catabolic role of TLR-2 mediated by the NF-kappa B pathway in septic arthritis. Modulation of TLR-mediated signaling may be a potential therapeutic strategy for the prevention of postinfectious cartilage degradation in articular joints. (C) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29: 247-251, 2011