Interleukin-1beta induces interleukin-6 production through the production of prostaglandin E(2) in human osteoblasts, MG-63 cells.
This study was conducted to investigate the mechanism of interleukin-1beta (IL-1beta)-induced IL-6 production in human osteoblasts (MG-63 cells). Stimulation with IL-1beta resulted in the production of IL-6 and prostaglandin E(2) (PGE(2)). IL-6 production gradually increased and peaked 96 h after stimulation. IL-6 mRNA was detected between 4 and 72 h after IL-1beta stimulation. The patterns of PGE(2) production and the expression of cyclooxygenase-2 (COX-2) mRNA were biphasic after stimulation. Actinomycin D, cycloheximide, indomethacin, and NS-398 (COX-2 inhibitor) suppressed the production of IL-6 and PGE(2). Anti-PGE(2) antibody markedly reduced the production of IL-6. In addition, stimulation with 17-phenyl-PGE(2), a PGE receptor-1 (EP-1 receptor) agonist, led to the expression of IL-6 mRNA after pretreatment with IL-1beta. These findings indicate that IL-1beta-induced IL-6 production in MG-63 cells involves the following sequence of steps: IL-1beta-induced COX-2 activation, PGE(2) production, and EP-1 receptor signaling prior to IL-6 production.
Takaoka
Y
Y
Department of Pharmacology, Gifu Pharmaceutical University, Gifu, 502-8585, Japan.
Niwa
S
S
Nagai
H
H
D000906:Antibodies / Q000276:immunology; D001483:Base Sequence; D002460:Cell Line; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D017931:DNA Primers; D015232:Dinoprostone / Q000819:agonists / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D007527:Isoenzymes / Q000235:genetics; D007700:Kinetics; D008565:Membrane Proteins; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D000906:Antibodies; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D017931:DNA Primers; D007375:Interleukin-1; D015850:Interleukin-6; D007527:Isoenzymes; D008565:Membrane Proteins; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone