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Chemerin induces endothelial cell inflammation: activation of nuclear factor-kappa beta and monocyte-endothelial adhesion

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Dimitriadis, Georgios K., Kaur, Jaspreet, Adya, Raghu, Miras, Alexander D., Mattu, Harman S., Hattersley, John G., Kaltsas, Gregory, Tan, Bee K. and Randeva, Harpal S. (2018) Chemerin induces endothelial cell inflammation: activation of nuclear factor-kappa beta and monocyte-endothelial adhesion. Oncotarget, 9 . pp. 16678-16690. doi:10.18632/oncotarget.24659 ISSN 1949-2553.

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Official URL: https://doi.org/10.18632/oncotarget.24659

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Abstract

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.

Item Type: Journal Article
Alternative Title:
Subjects: Q Science > QP Physiology
R Medicine > RB Pathology
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Inflammation -- physiological aspects, Blood-vessels -- Diseases, Obesity, Non-insulin-dependent diabetes
Journal or Publication Title: Oncotarget
Publisher: Impact Journals LLC
ISSN: 1949-2553
Official Date: 30 March 2018
Dates:
DateEvent
30 March 2018Published
26 February 2018Accepted
Volume: 9
Page Range: pp. 16678-16690
DOI: 10.18632/oncotarget.24659
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access
Date of first compliant deposit: 21 March 2018
Date of first compliant Open Access: 22 March 2018
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
UNSPECIFIEDUniversity of Warwickhttp://dx.doi.org/10.13039/501100000741
UNSPECIFIEDGeneral Charities of the City of Coventry (GCCC)UNSPECIFIED
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