Expression and function of Toll-like receptors in peripheral blood mononuclear cells in patients with ankylosing spondylitis

Abstract

Ankylosing spondylitis (AS) is a common chronic inflammatory autoimmune disease. Toll-like receptors (TLRs) are involved in non-specific immunity. In the present study, the roles of TLRs in AS were investigated. The levels of inflammatory cytokines were detected by ELI SA and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expression levels of TLRs and nuclear factor-κB (NF-κB) signaling-associated factors were determined via RT-qPCR and western blot analyses. It was observed that the levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), C-reactive protein, TLR4 and TLR5 were increased in patients with AS, whereas those of IL-10 and TLR3 were decreased. Pomalidomide, a TNF-α release inhibitor, reduced the expression of IL-6, TNF-α, TLR4, TLR5 and phosphorylated-p65, and upregulated that of IL-10, TLR3 and p65 in peripheral blood mononuclear cells from patients with AS. Treatment of patients with infliximab, an anti-TNF-α monoclonal antibody, induced similar effects in vivo. In conclusion, it was revealed that inhibition of TNF-α suppressed inflammatory responses in patients with AS, increased the expression of TLR3 and decreased NF-κB signaling, and the expression of TLR4 and TLR5. The results indicated that TLRs and the NF-κB signaling pathway were involved in the regulation of inflammatory responses in AS. These findings provided insight into the mechanisms underlying the development of AS and potential novel therapeutic approaches.