C5a modulation of interleukin-1 beta-induced interleukin-6 production by human osteoblast-like cells.
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-1beta prior to C5a challenge at optimal concentrations (1.0 microg/ml C5a, 0.1 ng/ml IL-1beta). Cells simultaneously challenged with these concentrations of C5a and IL-1beta produced a 700% increase in IL-6 release relative to cells challenged with IL-1beta alone. Incubation of IL-1beta-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-1beta co-stimulation of IL-6. In addition, neither IL-1beta 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-1beta 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.
Bioregulation Laboratories, College of Dentistry, University of Nebraska Medical Center, Lincoln 68583-0740, USA.
J M
JM
Pobanz
R A
RA
Reinhardt
S
S
Koka
S D
SD
Sanderson
D016301:Alveolar Bone Loss / Q000276:immunology*; D000704:Analysis of Variance; D015936:Complement C5a / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007375:Interleukin-1 / Q000276:immunology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D015999:Multivariate Analysis; D010006:Osteoblasts / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D011951:Receptors, Complement / Q000096:biosynthesis; D012044:Regression Analysis; D014407:Tumor Cells, Cultured
D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D011951:Receptors, Complement; D015936:Complement C5a