APRIL promotes proliferation, secretion and invasion of fibroblast-like synoviocyte from rats with adjuvant induced arthritis

Abstract

Fibroblast-like synoviocyte (FLS) is the ultimate effectual cells in the pathogenesis of rheumatoid arthritis (RA). The current study was undertaken to investigate whether a proliferation-inducing ligand (APRIL) mediates the function of FLS in an animal model of RA. Rat adjuvant-induced arthritis (AA) was induced by intradermal injection of 0.1ml complete Freund's adjuvant. Synovium APRIL expression was detected by immunohistochemical analysis. The level of APRIL and matrix metalloproteinase (MMP)-9 were assayed by enzyme-linked immunosorbent assay. The expression of APRIL and its receptors (TACI, BCMA and BAFF-R) were assessed by immunofluorescence staining, flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR) and real-time RT-PCR. The effects of APRIL on the function of FLS were investigated by MTT, Quantibody Rat Inflammation Array 1 and transwell assays, respectively. A higher concentration of APRIL was detected in AA synovium homogenate compared with normal group. AA FLS expressed APRIL, TACI, BAFF-R and BCMA at the mRNA levels, whereas only APRIL and BCMA were confirmed to be expressed on membrane by flow cytometry. APRIL stimulated AA FLS proliferation, migration and invasion and the secretion of proinflammatory factors. In addition, FLS cocultured with APRIL-treated B cells or T cells had a significantly greater proliferation than FLS cultured alone. Neutralization of APRIL by the TACI-Ig fusion protein attenuated these stimulating effects of APRIL on FLS. Our data indicate that APRIL may act as an important mediator for facilitating the function of FLS. Blockade of APRIL thus may be a valuable adjunct in the treatment of RA.