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

Abstract

SummaryToll-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)-a 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-a, 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-a, 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-a 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-a, 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.

The genomics and genetics of ankylosing spondylitis

“…TLRs 4 and 5, 135,136 NLRP2 137 and CLEC4D 136 were all shown to be differentially expressed. Interestingly TLR4 was also shown to be up regulated at both RNA and protein level in AS PBMCs in a candidate gene study 138 as well as in degenerative intervertebral discs. 139 A role for the innate system in AS has long been postulated due to the proposed link between an as yet unknown pathogen and disease onset.…”

The role of human CD1c+ DCs at activating innate and adaptive immune responses

“…However, it remains to be determined if these innate cell populations are able to produce other IL-23-dependent cytokines such as IL-17F, IL-21 and IL-22, and which cell population would play a pathogenic or protective role in AS pathology. Interestingly, serum IL-12p70 levels have been reported to be elevated in AS patients compared to healthy controls (Yang et al, 2007). This finding indirectly suggested the role of Th1 cell activation in AS pathology.…”

The Relationship between Plasma sTRAIL Level and Disease Activity in Rheumatoid Arthritis

“…In a study by Yang ZX et al, serum sTRAIL levels were found to be significantly higher in patients with ankylosing spondylitis than those in RA patients and healthy controls but no significant difference was found between the RA group and healthy controls. As a reason for this finding, it is thought that sTRAIL might have largely passed to the synovial fluid and might be associated with apoptosis of synovial fibroblasts (14). In another study, sTRAIL level measured in RA synovial fluid was found to be significantly higher than that measured in osteoarthritis synovial fluid (19).…”

“…It is well known that TRAIL expression is enhanced in T cells and, as a result, monocyte apoptosis is increased in patients with SLE (7), whereas TRAIL-R1 is increased in ductal cells by IFN-g stimulation and these cells become susceptible to apoptosis in Sjogren's syndrome (8). It has been observed that the soluble TRAIL level is significantly higher in some neoplastic (9), infectious (10), and autoimmune diseases such as SLE (11)(12)(13) and ankylosing spondylitis (14,15).…”