Endothelin stimulates osteoblastic production of IL-6 but not macrophage colony-stimulating factor.
Endothelins (ET) are vasoactive polypeptide hormones that stimulate osteoblastic signal transduction events. Using MC3T3-E1 and primary osteoblasts, we studied ET effects on interleukin-6 (IL-6) and macrophage colony-stimulating factor (M-CSF) production. Enzyme-linked immunosorbent assay analysis showed a dose-dependent 3- to 3.5-fold increase in IL-6 with 100 nM ET-1 stimulation within 4 (primary osteoblasts) to 8 (MC3T3-E1) h. ET-3 was less effective at enhancing IL-6 production, with a maximal twofold increase after 100 nM ET-3 after 4 h. No significant increase in M-CSF production was noted with ET-1 or ET-3 in either cell type. Reverse-transcriptase polymerase chain reaction analysis demonstrated both ET(A) and ET(B) receptors on primary osteoblasts and only ET(A) receptors on MC3T3-E1. ET-1-stimulated IL-6 production was blocked by the inhibitor BQ-123, implicating ET(A) receptor involvement. Increased IL-6 protein was coupled with elevated IL-6 mRNA levels and a twofold increase in IL-6 message half-life.
Perkins
S L
SL
Department of Pathology, University of Utah Health Sciences Center, Salt Lake City 84132, USA.
Sarraj
E
E
Kling
S J
SJ
Kohan
D E
DE
D000818:Animals; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000494:pharmacology*; D019334:Endothelin-3 / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D017466:Receptors, Endothelin / Q000502:physiology*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
D019332:Endothelin-1; D019334:Endothelin-3; D015850:Interleukin-6; D012333:RNA, Messenger; D017466:Receptors, Endothelin; D016173:Macrophage Colony-Stimulating Factor