TNF-α Induces a Pro-Inflammatory Phenotypic Shift in Monocytes through ACSL1: Relevance to Metabolic Inflammation.
Cell Line
Chemokine CCL2
/ analysis
Coenzyme A Ligases
/ antagonists & inhibitors
Gene Expression Regulation
/ drug effects
HLA-DR Antigens
/ genetics
Humans
Inflammation
/ metabolism
Interleukin-1beta
/ analysis
Monocytes
/ cytology
NF-kappa B
/ metabolism
Phosphorylation
RNA Interference
RNA, Small Interfering
/ metabolism
Receptors, IgG
/ genetics
Triazenes
/ chemistry
Tumor Necrosis Factor-alpha
/ pharmacology
ACSL1
CD11c
Inflammation
Monocytes
TNF-α
Journal
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
ISSN: 1421-9778
Titre abrégé: Cell Physiol Biochem
Pays: Germany
ID NLM: 9113221
Informations de publication
Date de publication:
2019
2019
Historique:
received:
07
09
2018
accepted:
05
03
2019
entrez:
8
3
2019
pubmed:
8
3
2019
medline:
16
3
2019
Statut:
ppublish
Résumé
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. 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 RTPCR 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. 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. 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.
Sections du résumé
BACKGROUND/AIMS
OBJECTIVE
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
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 RTPCR 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
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
CONCLUSIONS
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.
Substances chimiques
CCL2 protein, human
0
Chemokine CCL2
0
HLA-DR Antigens
0
Interleukin-1beta
0
NF-kappa B
0
RNA, Small Interfering
0
Receptors, IgG
0
Triazenes
0
Tumor Necrosis Factor-alpha
0
triacsin C
6M6D4602I5
Coenzyme A Ligases
EC 6.2.1.-
ACSL1 protein, human
EC 6.2.1.3
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
397-407Subventions
Organisme : Kuwait Foundation for Advancement of Sciences (KFAS)
ID : RC-14016001, RA-2013-002, RA AM 2016-007
Pays : Kuwait
Organisme : L'Oréal-UNESCO FWIS 2017 fellowship grant
Pays : France
Informations de copyright
© Copyright by the Author(s). Published by Cell Physiol Biochem Press.
Déclaration de conflit d'intérêts
The authors declare no conflict of interests.