Suppression of osteoblast Toll-like receptor 2 signaling by endothelin-1.
Peripheral endothelin-1 (ET-1) levels are increased in chronic systemic disorders such as congestive cardiac failure, diabetes and chronic renal failure. Bone infections are also associated with poor prognoses in these conditions. In the present study, we examined the alterations in Toll-like receptor 2 (TLR2) signaling induced by ET-1 in an in vitro osteoblast cell model. The TLR2-positive murine osteoblast cell line MC3T3-E1 was treated with heat-killed Listeria monocytogenes (HKLM), a TLR2 ligand, in the presence or absence of ET-1. We examined TLR2 expression, intranuclear NF-κB phosphorylation and interleukin 6 (IL-6) production. ET-1 suppressed cell surface expression of TLR2, NF-κB phosphorylation and IL-6 production. As TLR2 represents an important mechanism by which osteoblasts recognize bacterial pathogens, a continuously elevated ET-1 status may impair pathogenic recognition by osteoblasts and consequently affect bone metabolism during infections.
Department of General Medicine, Surugadai Nihon University Hospital, Tokyo, Japan; Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan.
Ai
A
Suzaki
Shihoko
S
Komine-Aizawa
Satoshi
S
Hayakawa
D016475:3T3 Cells; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D019332:Endothelin-1 / Q000378:metabolism*; D005786:Gene Expression Regulation; D015850:Interleukin-6 / Q000378:metabolism; D008024:Ligands; D008089:Listeria monocytogenes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism
D019332:Endothelin-1; D015850:Interleukin-6; D008024:Ligands; D016328:NF-kappa B; D012333:RNA, Messenger; C498144:Rela protein, mouse; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D051996:Transcription Factor RelA
Endothelin-1; NF-κB; Toll-like receptor 2; interleukin 6; osteoblast