The antimicrobial peptide HBD-2 and the Toll-like receptors-2 and -4 are induced in synovial membranes in case of septic arthritis

• Published in: Virchows Archiv : an international journal of pathology Vol. 454; no. 6; pp. 685 - 694
• Main Authors: Varoga, D., Klostermeier, E., Paulsen, F., Wruck, C., Lippross, S., Brandenburg, L. O., Tohidnezhad, M., Seekamp, A., Tillmann, B., Pufe, T.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.06.2009; Springer; Springer Nature B.V
• Subjects: Arthritis, Infectious - metabolism; Arthritis, Infectious - microbiology; Arthritis, Infectious - pathology; Bacteria; beta-Defensins - biosynthesis; beta-Defensins - genetics; Biological and medical sciences; Cells, Cultured; Diseases of the osteoarticular system; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibroblasts - pathology; Gene Expression - drug effects; Interleukin-1 - pharmacology; Interleukin-6 - pharmacology; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Medicine; Medicine & Public Health; Membranes; Miscellaneous. Osteoarticular involvement in other diseases; Original Article; Pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Peptides; Pseudomonas aeruginosa; RNA, Messenger - metabolism; Staphylococcal Infections - complications; Staphylococcal Infections - metabolism; Staphylococcal Infections - pathology; Staphylococcus aureus; Staphylococcus aureus - isolation & purification; Staphylococcus aureus - physiology; Staphylococcus epidermidis - isolation & purification; Staphylococcus epidermidis - physiology; Synovial Membrane - metabolism; Synovial Membrane - microbiology; Synovial Membrane - pathology; Synovitis - metabolism; Synovitis - pathology; Toll-Like Receptor 2 - biosynthesis; Toll-Like Receptor 2 - genetics; Toll-Like Receptor 4 - biosynthesis; Toll-Like Receptor 4 - genetics; Tumor Necrosis Factor-alpha - pharmacology; Bacterial infection; Human β-defensin-2; Toll-like receptor; Antimicrobial peptide; Human; Toll like receptor 4; Peptides; Toll like receptor 2; Diseases of the osteoarticular system; Toll like receptor; Arthritis; Antimicrobial agent; Infection; Anatomic pathology; Synovial membrane; Bacteriosis; Defensin
• ISSN: 0945-6317; 1432-2307; 1432-2307
• DOI: 10.1007/s00428-009-0780-4

Septic arthritis is frequently observed especially in immune-compromised or chronically diseased patients and leads to functional impairment due to tissue destruction. Recently, production of antimicrobial peptides (AMP) was observed in articular cartilage after exposure to bacteria. This report examines the role of synoviocyte-derived AMPs in innate defense mechanisms of articular joints. Samples of healthy, low-grade synovialitis and septic synovial membranes were assessed for the expression of human β-defensin-2 (HBD-2) and Toll-like receptor-2 and -4 (TLR) by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). A stable synoviocyte line (K4IM) was used for in vitro experiments and assayed for endogenous HBD-2 and TLR production after exposure to inflammatory cytokines or bacterial supernatants by reverse transcription polymerase chain reaction (RT-PCR), real-time RT-PCR, Western blot, ELISA, and dual luciferase assay. Healthy human synovial membranes and cultured synoviocytes are able to produce HBD-2 and TLR-1–5 at basal expression levels. Samples of bacteria-colonized synovial membranes produce higher levels of HBD-2 when compared with samples of healthy tissues. K4IM synoviocytes exposed to Staphylococcus aureus , Pseudomonas aeruginosa , or proinflammatory cytokines demonstrated a clear HBD-2 transcription and protein induction. TLR-2 and -4 are known to have a critical role in the recognition of gram-positive and gram-negative bacteria in epithelia and are induced in mesenchymal synoviocytes after bacterial exposure on transcription and on protein level. This report demonstrates an unappreciated role of synovial membranes: samples of septic synovial membranes and cultured synoviocytes exposed to bacteria produce increased amounts of the AMP HBD-2 and the bacteria recognition receptors TLR-2 and -4. The induction of anti-inflammatory pathways in infected synoviocytes suggests involvement in intra-articular defense mechanisms.