Abstract
BACKGROUND: CD55 (decay-accelerating factor) is a complement-regulatory protein highly expressed on fibroblast-like synoviocytes (FLS). CD55 is also a ligand for CD97, an adhesion-type G protein-coupled receptor abundantly present on leukocytes. Little is known regarding the regulation of CD55 expression in FLS.
METHODS: FLS isolated from arthritis patients were stimulated with pro-inflammatory cytokines and Toll-like receptor (TLR) ligands. Transfection with polyinosinic-polycytidylic acid (poly(I:C)) and 5'-triphosphate RNA were used to activate the cytoplasmic double-stranded (ds)RNA sensors melanoma differentiation-associated gene 5 (MDA5) and retinoic acid-inducible gene-I (RIG-I). CD55 expression, cell viability, and binding of CD97-loaded beads were quantified by flow cytometry.
RESULTS: CD55 was expressed at equal levels on FLS isolated from patients with rheumatoid arthritis (RA), osteoarthritis, psoriatic arthritis and spondyloarthritis. CD55 expression in RA FLS was significantly induced by IL-1β and especially by the TLR3 ligand poly(I:C). Activation of MDA5 and RIG-I also enhanced CD55 expression. Notably, activation of MDA5 dose-dependently induced cell death, while triggering of TLR3 or RIG-I had a minor effect on viability. Upregulation of CD55 enhanced the binding capacity of FLS to CD97-loaded beads, which could be blocked by antibodies against CD55.
CONCLUSIONS: Activation of dsRNA sensors enhances the expression of CD55 in cultured FLS, which increases the binding to CD97. Our findings suggest that dsRNA promotes the interaction between FLS and CD97-expressing leukocytes.
Original language | English |
---|---|
Article number | e35606 |
Pages (from-to) | e35606 |
Journal | PLOS ONE |
Volume | 7 |
Issue number | 5 |
DOIs | |
Publication status | Published - 2012 |
Keywords
- Adult
- Aged
- Aged, 80 and over
- Antigens, CD/immunology
- Arthritis/immunology
- CD55 Antigens/biosynthesis
- Cell Communication/drug effects
- Cells, Cultured
- DEAD Box Protein 58
- DEAD-box RNA Helicases/immunology
- Female
- Fibroblasts/immunology
- Humans
- Interferon Inducers/pharmacology
- Interferon-Induced Helicase, IFIH1
- Interleukin-1beta
- Leukocytes/immunology
- Male
- Middle Aged
- Poly I-C/pharmacology
- RNA, Double-Stranded
- Receptors, G-Protein-Coupled
- Synovial Membrane/immunology
- Toll-Like Receptor 3/immunology
- Up-Regulation