title: The catabolic role of toll-like receptor 2 (TLR-2) mediated by the NF-κB pathway in septic arthritis.
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.
authors.affiliation: Medical School, Laboratory of Cytogenetics and Molecular Genetics, University of Thessaly, Larissa, Greece.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Papathanasiou
authors.forename: Konstantinos N
authors.initials: KN
authors.lastname: Malizos
authors.forename: Lazaros
authors.initials: L
authors.lastname: Poultsides
authors.forename: Theofilos
authors.initials: T
authors.lastname: Karachalios
authors.forename: Pagona
authors.initials: P
authors.lastname: Oikonomou
authors.forename: Aspasia
authors.initials: A
authors.lastname: Tsezou
mesh_terms: D000328:Adult; D001170:Arthritis, Infectious / Q000378:metabolism*; D019902:Chondrocytes / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D008875:Middle Aged; D000072000:NF-KappaB Inhibitor alpha; D012333:RNA, Messenger / Q000378:metabolism; D013203:Staphylococcal Infections / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism*
chemical_list: D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; D012333:RNA, Messenger; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13