C5a modulation of interleukin-1β-induced interleukin-6 production by human osteoblast-like cells

John M. Pobanz, Richard A. Reinhardt, Sreenivas Koka, Sam D. Sanderson

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Periodontal bone resorption is controlled by osteoblast products, including interleukin (IL)-6, which are stimulated by other cytokines and complement components in the pro-inflammatory milieu. This study demonstrated that human osteoblast-like osteosarcoma cells (MG-63) responded to human recombinant (hr) C5a by releasing significant amounts of the bone-resorbing cytokine IL-6. C5a-induced release of IL-6 was enhanced 330% when cells were exposed to IL-1β prior to C5a challenge at optimal concentrations (1.0 μg/ml C5a, 0.1 ng/ml IL-1β). Cells simultaneously challenged with these concentrations of C5a and IL-1β produced a 700% increase in IL-6 release relative to cells challenged with IL-1β alone. Incubation of IL-1/β-treated cells with anti-human C5a receptor (C5aR) Ab resulted in a 78% suppression of the C5a-induced release of IL-6, but C5aR neutralization did not affect C5a/IL-1β co-stimulation of IL-6. In addition, neither IL-1β nor C5a significantly altered the other's cell-surface receptor relative to binding affinity or density. These results indicate that while MG-63 cells express functional C5aRs, the synergistic effect of C5a and IL-1β on osteoblast IL-6 production is probably controlled by post-receptor signaling events. C5a agonists and antagonist used to alter critical C5a concentrations may present a new point of therapeutic intervention for the treatment of inflammatory bone resorption such as is found in periodontitis.

Original languageEnglish (US)
Pages (from-to)137-145
Number of pages9
JournalJournal of Periodontal Research
Issue number3
StatePublished - Jun 2000


  • Cell surface molecules
  • Complement
  • Cytokines
  • Osteoblasts

ASJC Scopus subject areas

  • Periodontics


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