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Abstract
BackgroundThe aim of the study was to investigate the expression of the NEK7-NLRP3 inflammasome signaling pathway in the peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE), as well as its clinical significance.MethodsA total of 38 SLE patients and 33 healthy volunteers were recruited. Real time PCR and western blotting were performed to determine mRNA and protein levels of NEK7, NLRP3 inflammasome components (NLRP3, ASC, and Caspase-1), and downstream cytokines (IL-1b and IL-18) in PBMCs from the two groups. ELISA was used to detect serum levels of IL-1b and IL-18. The same methods were used to detect changes in the above indices in the 25 SLE patients after treatment. Correlations between clinical and laboratory parameters were also analyzed.ResultsCompared to those in healthy controls, levels of NEK7, NLPR3, and ASC were lower in SLE patients; however, Caspase-1, IL-1b, and IL-18 were expressed at higher levels. mRNA levels of NEK7, NLRP3, and ASC were inversely correlated with disease activity, whereas a positive correlation was observed with IL-1b and IL-18. After treatment, mRNA levels of NEK7 and NLRP3 increased, whereas Caspase-1, IL-1b, and IL-18 decreased significantly. Compared to those in SLE patients without renal damage, patients with lupus nephritis (LN) exhibited lower mRNA levels of NEK7, NLRP3, and ASC but higher levels of Caspase-1, IL-1b, and IL-18.ConclusionsResults indicate that the expression of the NEK7-NLRP3 complex might play a protective role in the pathogenesis of SLE and is inversely correlated with disease activity. A positive effect of NEK7 on NLRP3 was observed, and the low expression of NLRP3 in SLE patients might be related to the low expression of NEK7. Overexpression of Caspase-1 in SLE patients mediates the maturation and release of IL-1b and IL-18, and contributes to the pathogenesis of SLE and LN.
Highlights
The aim of the study was to investigate the expression of the NIMA-related kinase 7 (NEK7)-NLRP3 inflammasome signaling pathway in the peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE), as well as its clinical significance
MRNA levels of NEK7, NLRP3 inflammasome components, and downstream cytokines in PBMC from SLE patients and healthy controls The mRNA expression of NEK7, NLRP3 inflammasome components (NLRP3, ASC, Caspase-1), and downstream cytokines (IL-1b, IL-18) in PBMCs from SLE patients and healthy controls was detected by real time-PCR
Results demonstrated that levels of NEK7 and NLRP3 were lower in PBMCs from SLE patients
Summary
The aim of the study was to investigate the expression of the NEK7-NLRP3 inflammasome signaling pathway in the peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE), as well as its clinical significance. The NLRP3 inflammasome can be activated by a variety of pathogens such as bacteria, viruses, metabolic toxins, saturated fatty acids, amyloid peptides, adenosine triphosphate, and urate salts, and is related to the development of many diseases [3]. It consists of three parts, NLRP3, ASC, and Caspase-1; activation of NLRP3 further activates the inflammatory caspase protein kinase (Caspase-1), resulting in production of the active forms of the inflammatory cytokines interleukin-1b (IL-1b) and interleukin-18 (IL-18), which plays an important role in inflammation and the immune response
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