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Interleukin-1 Induces the Release of Lubricating Phospholipids from Human Osteoarthritic Fibroblast-like Synoviocytes
- Source :
- International Journal of Molecular Sciences; Volume 23; Issue 5; Pages: 2409
- Publication Year :
- 2022
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2022.
-
Abstract
- (1) Background: Synovial fluid (SF) from knee joints with osteoarthritis (OA) has increased levels of phospholipids (PL). We have reported earlier that TGF-ß and IGF-1 stimulate fibroblast-like synoviocytes (FLS) to synthesize increased amounts of PLs. The current study examined whether IL-1ß induces the release of PLs in FLS and the underlying mechanism. (2) Methods: Cultured human OA FLS were treated with IL-1ß alone and with pathway inhibitors or with synthetic liver X receptor (LXR) agonists. Cholesterol hydroxylases, ABC transporters, apolipoproteins (APO), LXR, sterol regulatory binding proteins (SREBPs), and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) were analyzed by RT-PCR, Western blot, and ELISA. The release of radiolabeled PLs from FLS was determined, and statistical analysis was performed using R (N = 5–9). (3) Results: Like synthetic LXR agonists, IL-1ß induced a 1.4-fold greater release of PLs from FLS. Simultaneously, IL-1ß upregulated the level of the PL transporter ABCA1 and of cholesterol hydroxylases CH25H and CYP7B1. IL-1ß and T0901317 stimulated the expression of SREBP1c, whereas only T0901317 enhanced SREBP2, HMGCR, APOE, LXRα, and ABCG1 additionally. (4) Conclusions: IL-1ß partially controls PL levels in OA-SF by affecting the release of PLs from FLS. Our data show that IL-1ß upregulates cholesterol hydroxylases and thus the formation of oxysterols, which, as natural agonists of LXR, increase the level of active ABCA1, in turn enhancing the release of PLs.
- Subjects :
- Benzylamines
Interleukin-1beta
Organic Chemistry
Cytochrome P450 Family 7
General Medicine
Benzoates
Synoviocytes
Catalysis
Computer Science Applications
Inorganic Chemistry
Gene Expression Regulation
phospholipids
interleukin
LXR
ABCA1
cholesterol hydroxylase
CH25H
CYP7B1
FLS
synovial fibroblasts
osteoarthritis
Osteoarthritis
Steroid Hydroxylases
Synovial Fluid
polycyclic compounds
Humans
lipids (amino acids, peptides, and proteins)
Physical and Theoretical Chemistry
Molecular Biology
Cells, Cultured
Phospholipids
Spectroscopy
ATP Binding Cassette Transporter 1
Liver X Receptors
Subjects
Details
- Language :
- English
- ISSN :
- 14220067
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences; Volume 23; Issue 5; Pages: 2409
- Accession number :
- edsair.doi.dedup.....0a6bdaca2bb8625bd813fc6b1bc741fb
- Full Text :
- https://doi.org/10.3390/ijms23052409