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C5a modulation of interleukin‐1 β ‐induced interleukin‐6 production by human osteoblast‐like cells
Author(s) -
Pobanz John M.,
Reinhardt Richard A.,
Koka Sreenivas,
Sanderson Sam D.
Publication year - 2000
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1034/j.1600-0765.2000.035003137.x
Subject(s) - c5a receptor , osteoblast , bone resorption , cytokine , interleukin , receptor , chemistry , microbiology and biotechnology , endocrinology , medicine , biology , immunology , complement system , in vitro , immune system , biochemistry
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‐1β‐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.