Upregulation of the C/EBP β LAP isoform could be due to decreased TNFAIP3/TNIP1 expression in the peripheral blood mononuclear cells of patients with systemic lupus erythematosus

Mod Rheumatol. 2017 Jul;27(4):657-663. doi: 10.1080/14397595.2016.1232331. Epub 2016 Sep 23.

Abstract

Objectives: We aimed to examine CCAAT/enhancer-binding protein β (C/EBP β), TNF-alpha-induced protein 3 (TNFAIP3), and TNFAIP3-interacting protein 1 (TNIP1) expression in peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) patients to assess their relationship in SLE pathogenesis.

Methods: C/EBP β, TNIP1, and TNFAIP3 expression was assessed in PBMCs from 20 SLE patients and 20 controls by western blotting. The correlation between C/EBP β/TNFAIP3/TNIP1 expression and SLE disease activity was determined by Spearman's rank. C/EBP β, TNIP1, and TNFAIP3 levels in THP-1 cells, THP-1 cells transfected with plasmids encoding TNFAIP3 shRNA, and THP-1 cells infected with lentiviral vectors encoding TNIP1 shRNA were assessed by western blotting.

Results: C/EBP β LAP isoform expression was increased and LIP/TNFAIP3/TNIP1 expression was decreased in SLE patients. LAP expression was positively correlated with SLE disease activity; TNFAIP3 and TNIP1 expression was negatively correlated with SLE disease activity. LAP expression was increased in SLE patients with proteinuria and elevated anti-dsDNA antibody, as well as in THP-1 cells transfected with plasmids encoding TNFAIP3 shRNA and THP-1 cells infected with lentiviral vectors encoding TNIP1 shRNA.

Conclusions: C/EBP β/TNFAIP3/TNIP1 is associated with SLE activity. The upregulated expression of C/EBP β LAP could be caused by reduced TNFAIP3/TNIP1 expression.

Keywords: Autoimmunity; CCAAT/enhancer-binding protein β; SLE; TNF-alpha-induced protein 3; TNFAIP3-interacting protein 1.

MeSH terms

  • Adolescent
  • Adult
  • CCAAT-Enhancer-Binding Protein-beta / genetics
  • CCAAT-Enhancer-Binding Protein-beta / metabolism*
  • Cell Line
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Female
  • Humans
  • Leukocytes, Mononuclear / metabolism*
  • Lupus Erythematosus, Systemic / genetics
  • Lupus Erythematosus, Systemic / metabolism*
  • Male
  • Middle Aged
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism*
  • Tumor Necrosis Factor alpha-Induced Protein 3 / genetics
  • Tumor Necrosis Factor alpha-Induced Protein 3 / metabolism*
  • Up-Regulation*
  • Young Adult

Substances

  • CCAAT-Enhancer-Binding Protein-beta
  • DNA-Binding Proteins
  • Protein Isoforms
  • TNIP1 protein, human
  • TNFAIP3 protein, human
  • Tumor Necrosis Factor alpha-Induced Protein 3