Toll-Like Receptor Expression is Necessary for Synovial Type II Cells to Respond to LPS: a Potential Mechanism of Reactive Arthritis (101.14)

Abstract

Abstract Reactive arthritis is predominantly associated with abnormal immune reactivity to gram-negative bacterial infections in children and young adults, but the precise molecular mechanism of the pathology remains unknown. Our previous results indicated fibroblast-like synovial cells (FLSC) express inducible Toll-like receptors (TLR). In this study we investigated the potential relationship of synovial cell TLR-dependent responses to the pathologen of reactive arthritis. To define TLR positive synovial cell subtypes, cell specific surface markers and flow cytometry were used both to isolate and to characterize the cells from mouse synovial tissues. Using synovial cell cultures and anti-TLR oligonucleotides, we examined whether the synovial immunological responses to LPS is dependent on TLR expression. Our data shows partial of FLSC were consecutive positive for TLR4, and inducible by LPS or cytokines. These cells were different from typical fibroblasts which are TLR4 negative. The TLR4+ FLSCs contribute approximately thirty percent of the isolated FLSC population, and sensitive to gram-negative bacterial endotoxin to produce inflammatory cytokines. Suppression of TLR4 expression on the cell surface significantly decreased the production of LPS-induced cytokines. The findings suggest synovial cells may orchestrate the immunological responses to bacterial components via TLR-based mechanisms.