Journalartikel

Jahr der Veröffentlichung: 2022

Zeitschrift: International Journal of Molecular Sciences

Bandnummer: 23

Heftnummer: 5

ISSN: 1661-6596

eISSN: 1422-0067

Open Access Status: Gold

DOI Link: https://doi.org/10.3390/ijms23052409

Verlag: MDPI

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, LXR alpha, 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.

Harvard-Zitierstil: Thottakkattumana Parameswaran, V., Hild, C., Eichner, G., Ishaque, B., Rickert, M. and Steinmeyer, J. (2022) Interleukin-1 Induces the Release of Lubricating Phospholipids from Human Osteoarthritic Fibroblast-Like Synoviocytes, International Journal of Molecular Sciences, 23(5), Article 2409. https://doi.org/10.3390/ijms23052409

APA-Zitierstil: Thottakkattumana Parameswaran, V., Hild, C., Eichner, G., Ishaque, B., Rickert, M., & Steinmeyer, J. (2022). Interleukin-1 Induces the Release of Lubricating Phospholipids from Human Osteoarthritic Fibroblast-Like Synoviocytes. International Journal of Molecular Sciences. 23(5), Article 2409. https://doi.org/10.3390/ijms23052409