Interleukin-1? and cathepsin D modulate formation of the terminal complement complex in cultured human disc tissue

Abstract Purpose Formation of terminal complement complex (TCC), a downstream system activation product inducing inflammatory processes and cell lysis, has been identified in degenerated discs. However, it remains unclear which molecular factors regulate during disc degeneration (DD). This study investigated possible involvement the pro-inflammatory cytokine interleukin-1? (IL-1?) lysosomal protease cathepsin D (CTSD). Methods Disc biopsies were collected from patients suffering DD ( n = 43) adolescent idiopathic scoliosis (AIS, 13). Standardized tissue punches isolated cells nucleus pulposus (NP), annulus fibrosus (AF) endplate (EP) stimulated with 5% human serum (HS) alone or combination IL-1?, CTSD zymosan. TCC formation modulation by regulatory proteins CD46, CD55 CD59 analysed. Results In cultures, IL-1? stimulation decreased percentage + AF EP P < 0.05), whereas significantly increased deposition NP 0.01) zymosan 0.05). Overall, expression all culture Moreover, cellular was HS concentration dependent but unaffected Conclusion These results suggest functional relevance modulating DD, differences between regions. Although strong may represent degeneration-associated event, inhibit it. contrast, shown to be triggered CTSD, indicating multifunctional pathophysiology.