The neuropeptide VIP potentiates IL-6 production induced by proinflammatory osteotropic cytokines in calvarial osteoblasts and the osteoblastic cell line MC3T3-E1.
Skeletal turnover is orchestrated by a complex network of regulatory factors. Lately, regulation of bone metabolism through neuro-osteological interactions has been proposed. Here, we address the question whether IL-6 production can be affected by interactions between the neuropeptide VIP and proinflammatory, bone-resorbing cytokines. By using calvarial osteoblasts, we showed that IL-1beta increased IL-6 production time- and concentration-dependently, and that these effects were potentiated by VIP. Furthermore, IL-1beta stimulated IL-6 promoter activity in the osteoblastic cell line MC3T3-E1 stably transfected with a human IL-6 promoter/luciferase construct, and both VIP, and the related neuropeptide PACAP-38, increased the effect of IL-1beta in a synergistic manner. The IL-6 protein release from calvarial osteoblasts was also stimulated by the osteoclastogenic, proinflammatory cytokines IL-11, LIF, OSM, IL-17, TGF-beta, and TNF-alpha. All effects, except for that of TNF-alpha, were synergistically potentiated by VIP. These findings further support the role of neuropeptides, and the presence of neuro-immunological interactions, in bone metabolism.
Persson
Emma
E
Department of Oral Cell Biology, Umeå University, Umeå, Sweden. emma.persson@odont.umu.se
Lerner
Ulf H
UH
D016475:3T3 Cells; D000818:Animals; D016207:Cytokines / Q000502:physiology*; D018836:Inflammation Mediators / Q000502:physiology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D012886:Skull / Q000166:cytology / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D014660:Vasoactive Intestinal Peptide