Journal article

Publication year: 2022

Journal: International Journal of Molecular Sciences

Volume number: 23

Issue number: 5

ISSN: 1661-6596

eISSN: 1422-0067

Open access status: Gold

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

Publisher: 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 Citation style: 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 Citation style: 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