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 ELISA 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.

Identification of immune related cells and crucial genes in the peripheral blood of ankylosing spondylitis by integrated bioinformatics analysis

“…Previous studies found that Th1 and Th2 chemoattractants played a cooperative role in the development of AS. Th1 and Th2 chemokine levels decreased under etanercept, a TNF-a blocker, to improve the activity and functional capacity of AS patients (Ergin et al, 2011;Wang et al, 2016;Zhang et al, 2018).…”

Associations of toll‐like receptor 4 and 2 gene polymorphisms with susceptibility to ankylosing spondylitis: A meta‐analysis

“…And after treatment with anti-TNF drugs, the gene expression of TLR4 significantly decreased (Assassi et al, 2011). Similarly, another study also reported that TLR4 mRNA significantly increased in AS patients (Zhang et al, 2019). All the aforementioned reports suggested that TLR4 gene might be a contributor to AS.…”

Andrographolide Against Lung Cancer-New Pharmacological Insights Based on High-Throughput Metabolomics Analysis Combined with Network Pharmacology

“…IgM with a large molecular weight cannot pass through blood vessel walls, and can be used for early diagnosis of body infections (Macpherson et al, 2008;Liu and May 2016;Hansen et al, 2019;Zhou et al, 2019). TLR4 is a member of the Toll-like receptor superfamily that plays a biological role in the form of binding to ligands (Zhang J. et al, 2019). Tumor cells can release a large number of cytokines in the process of immune remodeling, such as IL-10 and TGF-β, the latter can weaken the killing activity of cytotoxic T lymphocytes and natural killer cells, evading immune surveillance and promote tumor metastasis (Solinas et al, 2010;Wei et al, 2010;Bellomo et al, 2016;Anguiano-Hernandez et al, 2019;Dong et al, 2019).…”