TNF-α induces a pro-inflammatory phenotypic shift in monocytes through ACSL1 : Relevance to metabolic inflammation

Show full item record



Permalink

http://hdl.handle.net/10138/312718

Citation

Al-Rashed , F , Ahmad , Z , Iskandar , M A , Tuomilehto , J , Al-Mulla , F & Ahmad , R 2019 , ' TNF-α induces a pro-inflammatory phenotypic shift in monocytes through ACSL1 : Relevance to metabolic inflammation ' , Cellular Physiology and Biochemistry , vol. 52 , no. 3 , pp. 397-407 . https://doi.org/10.33594/000000028

Title: TNF-α induces a pro-inflammatory phenotypic shift in monocytes through ACSL1 : Relevance to metabolic inflammation
Author: Al-Rashed, F.; Ahmad, Z.; Iskandar, M.A.; Tuomilehto, J.; Al-Mulla, F.; Ahmad, R.
Contributor organization: Clinicum
Date: 2019
Language: eng
Number of pages: 11
Belongs to series: Cellular Physiology and Biochemistry
ISSN: 1015-8987
DOI: https://doi.org/10.33594/000000028
URI: http://hdl.handle.net/10138/312718
Abstract: Background/Aims: TNF-α-mediated pro-inflammatory phenotypic change in monocytes is known to be implicated in the pathogenesis of metabolic inflammation and insulin resistance. However, the mechanism by which TNF-α-induces inflammatory phenotypic shift in monocytes is poorly understood. Since long-chain acyl-CoA synthetase 1 (ACSL1) is associated with inflammatory monocytes/macrophages, we investigated the role of ACSL1 in the TNF-α-driven inflammatory phenotypic shift in the monocytes. Methods: Monocytes (Human monocytic THP-1 cells) were stimulated with TNF-α. Inflammatory phenotypic markers (CD16, CD11b, CD11c and HLA-DR) expression was determined with real time RT-PCR and flow cytometry. IL-1β and MCP-1 were determined by ELISA. Signaling pathways were identified by using ACSL1 inhibitor, ACSL1 siRNA and NF-κB reporter monocytic cells. Phosphorylation of NF-κB was analyzed by western blotting and flow cytometry. Results: Our data show that TNF-α induced significant increase in the expression of CD16, CD11b, CD11c and HLA-DR. Inhibition of ACSL1 activity in the cells with triacsin C significantly suppressed the expression of these inflammatory markers. Using ACSL-1 siRNA, we further demonstrate that TNF-α-induced inflammatory markers expression in monocytic cells requires ACSL1. In addition, IL-1b and MCP-1 production by TNF-α activated monocytic cells was significantly blocked by the inhibition of ACSL-1 activity. Interestingly, elevated NF-κB activity resulting from TNF-α stimulation was attenuated in ACSL1 deficient cells. Conclusion: Our findings provide an evidence that TNF-α-associated inflammatory polarization in monocytes is an ACSL1 dependent process, which indicates its central role in TNF-α-driven metabolic inflammation. © 2019 The Author(s).
Subject: ACSL1
CD11c
Inflammation
Monocytes
TNF-α
CD11b antigen
CD16 antigen
glycoprotein p 15095
HLA DR11 antigen
immunoglobulin enhancer binding protein
interleukin 1beta
long chain fatty acid coenzyme A ligase
long chain fatty acid coenzyme A ligase 1
monocyte chemotactic protein 1
small interfering RNA
tumor necrosis factor
unclassified drug
ACSL1 protein, human
CCL2 protein, human
coenzyme A ligase
Fc receptor
HLA DR antigen
triacsin C
triazene derivative
Article
controlled study
enzyme linked immunosorbent assay
flow cytometry
human
human cell
macrophage
metabolic disorder
monocyte
phenotype
polarization
priority journal
protein analysis
protein expression
protein function
protein phosphorylation
protein secretion
protein synthesis
quantitative analysis
real time polymerase chain reaction
signal transduction
staining
THP-1 cell line
Western blotting
antagonists and inhibitors
cell line
chemistry
cytology
drug effect
gene expression regulation
genetics
inflammation
metabolism
pathology
phosphorylation
RNA interference
Cell Line
Chemokine CCL2
Coenzyme A Ligases
Gene Expression Regulation
HLA-DR Antigens
Humans
Interleukin-1beta
NF-kappa B
Phosphorylation
Receptors, IgG
RNA Interference
RNA, Small Interfering
Triazenes
Tumor Necrosis Factor-alpha
1182 Biochemistry, cell and molecular biology
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: publishedVersion


Files in this item

Total number of downloads: Loading...

Files Size Format View
000028.pdf 2.875Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record