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Crosstalk between miR-146a and pro-inflammatory cytokines in patients with systemic lupus erythematosus

Basima A El-Akhras1, Roba M Talaat1, Samir A El-Masry1

  • 1Molecular Biology Department, Genetic Engineering and Biotechnology Research Institute, 392053Sadat City University, Egypt.

International Journal of Immunopathology and Pharmacology
|February 5, 2023
PubMed

Insights

microRNA-146a (miR-146a) is elevated in systemic lupus erythematosus (SLE) patients, acting as a potential biomarker. Its expression correlates with disease severity and specific cytokine profiles, suggesting a complex role in lupus inflammation.

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by immune system dysregulation and organ damage.
  • microRNA-146a (miR-146a) is implicated in immune responses and inflammation, making it a candidate for investigation in autoimmune conditions like SLE.
  • Understanding the role of miR-146a and associated cytokines in SLE pathogenesis is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the expression levels of miR-146a in patients with SLE compared to healthy controls.
  • To analyze the association between miR-146a expression, pro-inflammatory cytokines (IL-1β, IL-6, IL-8, IL-17, TNF-α), and clinical manifestations in SLE.
  • To evaluate the potential of miR-146a as a diagnostic or prognostic biomarker for SLE.

Main Methods:

  • Quantitative real-time PCR (RT-qPCR) was used to measure miR-146a expression in peripheral blood mononuclear cells (PBMCs) from 113 SLE patients and 104 healthy volunteers.
  • Plasma levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, IL-17, TNF-α) were quantified using enzyme-linked immunosorbent assay (ELISA).
  • Statistical analyses, including ROC curve analysis, were performed to assess diagnostic accuracy and correlations between parameters and disease activity.

Main Results:

  • miR-146a expression was significantly higher in SLE patients than in healthy controls (p < 0.05), with 91% sensitivity and 70% specificity.
  • Significant differences in cytokine levels were observed: IL-1β, IL-6, and IL-17 were elevated (p < 0.001), while IL-8 and TNF-α were decreased (p < 0.001) in SLE patients.
  • Upregulation of miR-146a and TNF-α was associated with severe SLE disease activity, and miR-146a expression positively correlated with IL-6 levels.

Conclusions:

  • Elevated miR-146a serves as a potential biomarker for SLE.
  • The observed cytokine profile (reduced IL-8/TNF-α, elevated IL-1β/IL-6/IL-17) suggests a dual role for miR-146a in modulating inflammation in SLE.
  • Further research is warranted to elucidate the precise mechanisms of miR-146a and its therapeutic potential in SLE.
Keywords:
miR-146apro-inflammatory cytokinessystemic lupus erythematosus

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