Receptor activator of nuclear factor kappaB ligand is a novel inducer of tissue factor in macrophages.
نویسندگان
چکیده
RATIONALE Although recent studies have suggested a role for the receptor activator of nuclear factor κB ligand (RANKL) in the late stages of atherosclerosis (eg, plaque destabilization and rupture), the underlying mechanisms and subsequent events are unclear. OBJECTIVE Because blood clotting is common after plaque rupture, we hypothesized that RANKL influenced tissue factor (TF) expression and activity to initiate the coagulation cascade. METHODS AND RESULTS RANKL increased the TF mRNA level and procoagulant activity in macrophages, as determined by semiquantitative reverse transcription polymerase chain reaction (semiquantitative RT-PCR) and a chromogenic assay. TF promoter analysis revealed that AP-1 and Egr-1 are responsible for RANKL-induced TF transcription. In addition, RANKL increased phosphorylation of c-Jun NH(2)-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK)1/2. RANKL-induced TF expression was attenuated by JNK- and MEK1-specific inhibitors and by small interfering RNA knockdown of c-Jun and Egr-1. CONCLUSION Our results indicate that RANKL induces TF in macrophages mainly through the cooperative action of AP-1 and Egr-1 via JNK and ERK1/2 pathways. These findings provide strong mechanistic support for the role of RANKL in the thrombogenicity of atherosclerotic plaques.
منابع مشابه
Receptor Activator of Nuclear Factor Kappa B Ligand (RANKL) Levels in Peri-Implant Crevicular Fluid
Background: Receptor activator of nuclear factor kappa B ligand (RANKL) is one of the key cytokines in the induction of osteoclastogenesis both in vitro and in vivo.Several reports indicated the presence of sRANKL in gingival crevicular fluid of patients with periodontal diseases. Objective: To determine the presence of RANKL in peri-implant crevicular fluid samples of implants with peri-implan...
متن کاملReceptor Activator of Nuclear Factor B Ligand Is a Novel Inducer of Tissue Factor in Macrophages
متن کامل
Combined Hydroxyapatite Scaffold and Stem Cell from Human Exfoliated Deciduous Teeth Modulating Alveolar Bone Regeneration via Regulating Receptor Activator of Nuclear Factor-Κb and Osteoprotegerin System
Background: Tissue engineering using Stem cell from Human Exfoliated Deciduous Teeth (SHED) and a natural biomaterials biomaterial scaffold has become a promising therapy for the alveolar bone defect. The aim of this study was to analyze the Osteoprotegerin (OPG) and Receptor Activator of NF-Κb ligand (RANKL) expression after the application of Hydroxyapatite scaffold and SHED.Methods: A labora...
متن کاملRANKL is a mediator of bone resorption in idiopathic hypercalciuria.
BACKGROUND AND OBJECTIVES This study aimed to determine the expression of osteoprotegerin, receptor activator of nuclear factor kappaB ligand, interleukin-1alpha, transforming growth factor-beta, and basic fibroblast growth factor in stone-forming patients with idiopathic hypercalciuria. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Immunohistochemical analysis was performed in undecalcified ...
متن کاملBone morphogenetic protein 2 stimulates osteoclast differentiation and survival supported by receptor activator of nuclear factor-kappaB ligand.
Bone is a major storage site for TGFbeta superfamily members, including TGFbeta and bone morphogenetic proteins. It is believed that these cytokines are released from bone during bone resorption. Recent studies have shown that both RANKL and macrophage colony-stimulating factor are two essential factors produced by osteoblasts for inducing osteoclast differentiation. In the present study we exa...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Circulation research
دوره 107 7 شماره
صفحات -
تاریخ انتشار 2010