Chemerin induces endothelial cell inflammation: activation of nuclear factor-kappa beta and monocyte-endothelial adhesion
نویسندگان
چکیده
Chemerin, a chemoattractant protein, acts via a G-protein coupled chemokine receptor, i.e. Chemokine like Receptor 1/ChemR23; levels of which are elevated in pro-inflammatory states such as obesity and type 2 diabetes mellitus (T2DM). Obesity and T2DM patients are at high risk of developing cardiovascular disorders such as atherosclerosis. We have reported that chemerin induces human endothelial cell angiogenesis and since dysregulated angiogenesis and endothelial dysfunction are hallmarks of vascular disease; we sought to determine the effects of chemerin on monocyte-endothelial adhesion, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a critical pro-inflammatory transcription factor. Human endothelial cells were transfected with pNF-kappaB-Luc plasmid. Chemerin induced NF-κB activation via the MAPK and PI3K/Akt pathways. Western blot analyses and monocyte-endothelial adhesion assay showed that chemerin increased endothelial cell adhesion molecule expression and secretion, namely E-selectin (Endothelial Selectin), VCAM-1 (Vascular Cell Adhesion Molecule-1) and ICAM-1 (Intracellular Adhesion Molecule-1), leading to enhancement of monocyte-endothelial adhesion. Additionally, we showed a synergistic response of the pro-inflammatory mediator, Interleukin-1β with chemerin induced effects. Chemerin plays an important role in endothelial inflammation, as it induces monocyte-endothelial adhesion, a critical step in the development of atherosclerosis.
منابع مشابه
The effect of microRNA-125 on the adhesion molecule expression of integrin beta2 and adhesive determination of endothelial cells isolated from human aorta to monocyte
Background: The immune-mediated responses in vascular cells may include the increased expression of endothelial adhesion molecules, leukocyte rolling and infiltration, cellular lipid dysregulation and vascular smooth muscle cells (VSMCs) differentiation. Investigating the cellular and molecular events involved in the rolling process is useful for treatment or prevention of the vessel stenosis es...
متن کاملVGB3 Induces Apoptosis by Inhibiting Phosphorylation of NF-κB p65 at Serine 536 in the Human Umbilical Vein Endothelial Cells
Background and objectives: Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inhibition results in an increase in apoptosis. It has been demonstrated that NF-κB subunit p65 phosphorylation at the IκB kinase phosphorylation site serine 536 (Ser536) is essential for the NF-κB nuclear translocation and activation. Therefore, NF-κB can be downregulated by suppressing its phosph...
متن کاملCurcumin Attenuates Nuclear Factor-κB, c-Jun N-Terminal Kinase and p38 in Tumor Necrosis Factor-α-Stimulated Endothelial Cells
Background and Objectives:Curcumin, a yellow pigment of turmeric in curry, has been reported to interfere with nuclear factor (NF)-κB. This study was designed to investigate the underlying pathway of the anti-inflammation effect of curcumin on endothelial cells. Materials and Methods:Human umbilical vein endothelial cells (HUVECs) were stimulated with tumor necrosis factor (TNF)-α (10 ng/mL). T...
متن کاملAntioxidants inhibit monocyte adhesion by suppressing nuclear factor-kappa B mobilization and induction of vascular cell adhesion molecule-1 in endothelial cells stimulated to generate radicals.
Cell adhesion to endothelial cells stimulated by tumor necrosis factor-alpha (TNF) is due to induction of surface receptors, such as vascular cell adhesion molecule-1 (VCAM-1). The antioxidant pyrrolidine dithiocarbamate (PDTC) specifically inhibits activation of nuclear factor-kappa B (NF-kappa B). Since kappa B motifs are present in VCAM-1 and intercellular adhesion molecule-1 (ICAM-1) promot...
متن کاملHEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Activated monocytes in sickle cell disease: potential role in the activation of vascular endothelium and vaso-occlusion
Sickle cell anemia is characterized by painful vaso-occlusive crises. It is hypothesized that monocytes are activated in sickle cell disease and can enhance vasoocclusion by activating endothelium. To test this hypothesis, human umbilical vein endothelial cells (HUVEC) and human microvascular endothelial cells (MVEC) with sickle and normal mononuclear leukocytes were incubated, and endothelial ...
متن کامل