Neutrophil extracellular traps induced by IL-8 aggravate atherosclerosis via activation NF-κB signaling in macrophages
Z An, J Li, J Yu, X Wang, H Gao, W Zhang, Z Wei… - Cell Cycle, 2019 - Taylor & Francis
Z An, J Li, J Yu, X Wang, H Gao, W Zhang, Z Wei, J Zhang, Y Zhang, J Zhao, X Liang
Cell Cycle, 2019•Taylor & FrancisHere, we sought to explore the underlying role of interleukin (IL)-8 in neutrophil extracellular
traps (NETs) formation during atherosclerosis (AS). The concentration of pro-inflammatory
cytokines IL-8, IL-6 and IL-1β was determined by enzyme-linked immunosorbent assay
(ELISA). NETs formation was evaluated by immunofluorescence and myeloperoxidase
(MPO)-DNA complex ELISA. The mRNA levels of IL-8 and Toll-like receptor 9 (TLR9) were
measured by quantitative real-time PCR (qRT-PCR). The phosphorylation levels of NF-κB …
traps (NETs) formation during atherosclerosis (AS). The concentration of pro-inflammatory
cytokines IL-8, IL-6 and IL-1β was determined by enzyme-linked immunosorbent assay
(ELISA). NETs formation was evaluated by immunofluorescence and myeloperoxidase
(MPO)-DNA complex ELISA. The mRNA levels of IL-8 and Toll-like receptor 9 (TLR9) were
measured by quantitative real-time PCR (qRT-PCR). The phosphorylation levels of NF-κB …
Abstract
Here, we sought to explore the underlying role of interleukin (IL)-8 in neutrophil extracellular traps (NETs) formation during atherosclerosis (AS).
The concentration of pro-inflammatory cytokines IL-8, IL-6 and IL-1β was determined by enzyme-linked immunosorbent assay (ELISA). NETs formation was evaluated by immunofluorescence and myeloperoxidase (MPO)-DNA complex ELISA. The mRNA levels of IL-8 and Toll-like receptor 9 (TLR9) were measured by quantitative real-time PCR (qRT-PCR). The phosphorylation levels of NF-κB p65 were detected by western blotting. The hematoxylin and eosin (H&E) staining of atherosclerotic lesion areas was performed in ApoE-deficiency mice.
Results showed that patients with AS showed higher serum levels of IL-8, a pro-inflammatory cytokine and NETs. IL-8 interacted with its receptor CXC chemokine receptor 2 (CXCR2) on neutrophils, leading to the formation of NETs via Src and extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinases (MAPK) signaling to aggravate AS progression in vivo. PMA-induced NETosis directly upregulated the TLR9/NF-κB pathway in macrophages and subsequently initiated the release of IL-8.
Our data reveal a neutrophil-macrophage interaction in AS progression, and indicate that NETs represent as a novel therapeutic target in treatment of AS and other cardiovascular diseases (CVD).
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