Effects of Ureaplasma urealyticum lipid-associated membrane proteins on rheumatoid arthritis synovial fibroblasts

Abstract

As an infectious agent might play a role in rheumatoid arthritis (RA) development, this study investigated effects of Ureaplasma urealyticum lipid-associated membrane proteins (UuLAMPs) on RA synovial fibroblast (RASF) proliferation, and tumour necrosis factor (TNF)-α and interleukin (IL)-1β production by THP-1 macrophages. Possible immunogenic proteins in UuLAMPs were identified. RASFs were cultured from synovial tissue from donors with RA. Serum samples from donors with/without RA and with/without U. urealyticum infection were used for immunogenicity analyses. THP-1 macrophages served as a model for synovial macrophages. TNF-α and IL-1β mRNA levels were assessed using reverse transcription-polymerase chain reaction; protein levels were estimated using enzyme-linked immunosorbent assay. UuLAMPs underwent separation and Western blot analyses. UuLAMPs (0.025-0.4 µg/ml) stimulated RASF proliferation in a dose- and time-dependent manner, and increased TNF-α and IL-1β levels in THP-1 macrophages. Several immunogenic UuLAMPs were identified, but antibodies to a 25 kDa protein were only found in RA patients with U. urealyticum infection. UuLAMPs might induce RASF proliferation and proinflammatory cytokine secretion in synovium from RA patients. A 25 kDa U. urealyticum protein might act as a cross-reactive antigen.