Increased expression of Toll-like receptor 4 in peripheral blood leucocytes and serum levels of some cytokines in patients with ankylosing spondylitis

Abstract

Toll-like receptor 4 (TLR4) is a member of the Toll-like receptor family, which can bridge innate and adaptive immune responses. Activation of the TLR4 signalling pathway may induce the release of proinflammatory cytokines such as tumour necrosis factor (TNF)-alpha and interleukin (IL)-12, which was considered to play an important role in pathogenesis of immune-mediated diseases. Ankylosing spondylitis (AS) is an immune-mediated disease whose aetiology remains unknown. The aim of the study was to investigate the expression of TLR4 and serum TNF-alpha, IL-12 and soluble tumour necrosis factor-related apoptosis-inducing ligand (sTRAIL) level in AS patients. The results indicated that TLR4 protein and mRNA levels were significantly higher in AS patients than in healthy controls; however, there was no significant difference between human leucocyte antigen (HLA)-B27-positive and -negative AS patients, as well as serum levels of TNF-alpha, IL-12 and sTRAIL. In addition, in HLA-B27-positive AS patients, TLR4 level showed close associations with the cytokines and laboratory parameters of disease activity [erythrocyte sedimentation rate (ESR) and plasma C-reactive protein (CRP)], respectively. Similarly, the strong associations between the cytokines or between IL-12 and ESR or CRP were observed in HLA-B27-positive AS patients. Interestingly, in HLA-B27-positive AS patients, TNF-alpha correlated significantly with ESR, but did not with CRP. In contrast, sTRAIL correlated with CRP, but did not with ESR. Among HLA-B27-negative patients, no close correlation was found. In our study, it was suggested that the abnormal activation of TLR4 signalling and serum TNF-alpha, IL-12 and sTRAIL may play a key role in the development and progression of AS, which may be dependent on the status of HLA-B27 antigen.

Figures

Fig. 1

The positive rates of Toll-like receptor 4 (TLR4) protein on peripheral blood cells. L = lymphocytes; M = monocytes; N = neutrophils. *P < 0·01 versus healthy controls.

Fig. 2

The normalized Toll-like receptor 4 (TLR4) mRNA level in peripheral blood mononuclear cells. P < 0·01 versus healthy controls.

Fig. 3

The association of Toll-like receptor 4 (TLR4) mRNA with the expression of TLR4 protein on monocytes from various populations. [a, b and c for human leucocyte antigen (HLA)-B27+, HLA-B27– ankylosing spondylitis (AS) patients and healthy controls, respectively].

Fig. 4

Relationship between serum cytokines and laboratory parameters of disease activity in human leucocyte antigen (HLA)-B27-positive patients with ankylosing spondylitis (AS).

Fig. 5

The correlations of expression of Toll-like receptor 4 (TLR4) protein on monocytes with erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) and cytokines [B for human leucocyte antigen (HLA)-B27– ankylosing spondylitis (AS) patients, others for HLA-B27+ AS patients].