The Effect of TLR9, MyD88, and NF-κB p65 in Systemic Lupus Erythematosus

Abstract

Purpose. This study was conducted to characterize the expression level of peripheral blood toll-like receptors 9 (TLR9), nuclear factor kappa-B protein 65 (NF-κB p65), and myeloid differentiation factor88 (MyD88) of active systemic lupus erythematosus (SLE) and analyse their clinical significance. Methods. The prospective cohort study enrolled 30 active SLE patients (SG1 group), 30 stable SLE patients (SG2 group), and 20 healthy individuals (RG group) in the First Affiliated Hospital of Hainan Medical University between January 2018 and June 2020. All SLE patients were treated with methylprednisolone tablets. Quantitative polymerase chain reaction (qPCR) was used to determine the levels of TLR9, MyD88, and NF-κB p65 in the peripheral blood mononuclear cell (PBMC). ELISA was adopted for the determination of serum interleukin (IL-6) and tumor necrosis factor-α (TNF-α). Results. Patients in SG1 showed the highest mRNA levels of TLR9, MyD88, and NF-κB p65, followed by SG2, and then RG. SG1 had the highest serum levels of IL-6 and TNF-α, followed by SG2 and RG. The level of TLR9 was positively correlated with the SLE disease activity index (SLEDAI) and negatively correlated with complement component 3 (C3) and complement component 4 (C4). MyD88 and NF-κB p65 were positively correlated with SLEDAI. Conclusion. Compared with a healthy status, SLE induces an increase in TLR9, MyD88, NF-κB p65, IL-6, and TNF-α levels, and the activation of the TLR9-MyD88-NF-κB p65 signal path was associated with the pathogenesis of SLE.

The exploration of shared genes and molecular mechanisms of systemic lupus erythematosus and atherosclerosis

“…The Let-7 family, one of the first small non-coding RNAs identified, is aberrantly expressed in inflammation-related diseases such as stroke, myocardial infarction, cardiac fibrosis, and AS. 32 Let-7e, a member of the let-7 family, is also a key regulator of endothelial function and inflammation that promotes NF-κB activation, thereby contributing to inflammatory factor expression and inflammatory responses in endothelial cells, suggesting that let-7e may play an essential pro-inflammatory role in the development of AS. 33 Other investigations discovered that let-7e expression was elevated in samples from lupus nephritis patients, and its overexpression was capable of inhibiting TNFAIP3 expression, promoting the activation of NF-κB, and inducing the production of pro-inflammatory cytokines.…”

TLR9 regulates the autophagy–lysosome pathway to promote dendritic cell maturation and activation by activating the TRAF6‐cGAS‐STING pathway

“…12 Studies have reported a significant upregulation of TLR9 in peripheral blood mononuclear cells (PBMCs) of SLE patients, with its expression positively correlated with the SLE disease activity index (SLEDA). 12 Moreover, TLR9 was excessively activated in SLE patients, and could lead to over-proliferation of mesangial cells to induce lupus nephritis. 13 Rao et al revealed that elevated TLR9 expression was positively associated with dsDNA in SLE patients and that loss of TLR9 resulted in markedly reduced IL-6, IL-10, and IL-1rα production in B cells.…”

“…Toll‐like receptors (TLRs) are a highly conserved group of pattern recognition receptors that plays a crucial role in the SLE progression by activating adaptive immunity signaling pathways 11 . Among the TLR family, TLR9 is particularly significant in regulating SLE progression by modulating inflammatory responses 12 . Studies have reported a significant upregulation of TLR9 in peripheral blood mononuclear cells (PBMCs) of SLE patients, with its expression positively correlated with the SLE disease activity index (SLEDA) 12 .…”

“…Among the TLR family, TLR9 is particularly significant in regulating SLE progression by modulating inflammatory responses 12 . Studies have reported a significant upregulation of TLR9 in peripheral blood mononuclear cells (PBMCs) of SLE patients, with its expression positively correlated with the SLE disease activity index (SLEDA) 12 . Moreover, TLR9 was excessively activated in SLE patients, and could lead to over‐proliferation of mesangial cells to induce lupus nephritis 13 .…”

Retracted: The Effect of TLR9, MyD88, and NF‐κB p65 in Systemic Lupus Erythematosus

“…This article has been retracted by Hindawi, as publisher, following an investigation undertaken by the publisher [ 1 ]. This investigation has uncovered evidence of systematic manipulation of the publication and peer-review process.…”