The catabolic role of toll-like receptor 2 (TLR-2) mediated by the NF-κB pathway in septic arthritis

✍ Scribed by Ioanna Papathanasiou; Konstantinos N. Malizos; Lazaros Poultsides; Theofilos Karachalios; Pagona Oikonomou; Aspasia Tsezou

• Publisher: Elsevier Science
• Year: 2010
• Tongue: English
• Weight: 394 KB
• Volume: 29
• Category: Article
• ISSN: 0736-0266
• DOI: 10.1002/jor.21239

✦ Synopsis

Abstract

Toll‐like receptors (TLRs) are involved in mediating cell activation on stimulation with microbial components. Our objective was to investigate the role of TLR‐2 mediated by the NF‐κB 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, IL‐1β, and IL‐6 mRNA levels, as well as p65 NF‐κB, IkBα, 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 nonphosphorylated p65 NF‐κB and IkBα protein levels and reduction in MMP‐13, IL‐1β, and IL‐6 expression. Our findings suggest the pro‐inflammatory and catabolic role of TLR‐2 mediated by the NF‐κB 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. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:247–251, 2011