C/ EBP β mRNA expression is upregulated and positively correlated with the expression of TNIP1/ TNFAIP3 in peripheral blood mononuclear cells from patients with systemic lupus erythematosus

Abstract

CCAAT/enhancer-binding protein β (C/EBP β) has important roles in numerous signaling pathways. The expression of the majority of regulators and target gene products of C/EBP β, including tumor necrosis factor α-induced protein 3 (TNFAIP3) and TNFAIP3-interacting protein 1 (TNIP1), are upregulated in patients with systemic lupus erythematosus (SLE). The aim of the present study was to investigate whether C/EBP β expression is associated with SLE pathogenesis and correlates with TNIP1 and TNFAIP3 expression. Quantitative reverse transcription-polymerase chain reaction analysis was used to assess the expression of C/EBP β, TNIP1, and TNFAIP3 mRNA in peripheral blood mononuclear cells (PBMC) from 20 patients with SLE and 20 healthy controls. Spearman's rank test was used to determine the correlation between C/EBP β expression and SLE disease activity, and that between C/EBP β expression and TNIP1/TNFAIP3 expression in PBMCs from patients with SLE. C/EBP β mRNA expression was markedly increased in patients with SLE compared with healthy controls. The expression of C/EBP β was positively correlated with the SLE disease activity index and negatively correlated with the serum level of complement components C3 and C4. In addition, C/EBP β mRNA expression was increased in PBMCs from SLE patients that were positive for antinuclear, anti-Smith and anti-nRNP antibodies, compared with the antibody negative SLE patients. Furthermore, the mRNA expression levels of C/EBP β in patients with SLE was positively correlated with TNIP1 and TNFAIP3 expression. The results of the current study suggest that the increased expression of C/EBP β in PBMCs and the interaction between C/EBP β and TNIP1/TNFAIP3 may be involved in the pathogenesis of SLE.

Keywords: CCAAT/enhancer-binding protein β; systemic lupus erythematosus; tumor necrosis factor α-induced protein 3; tumor necrosis factor α-induced protein 3-interacting protein 1.

Figure 1.

Relative expression of C/EBP β mRNA in PBMCs from patients with SLE. The C/EBP β mRNA expression levels in PBMCs from patients with SLE (n=20; circles) and healthy controls (n=20; triangles) were determined by reverse transcription-quantitative polymerase chain reaction. C/EBP β, CCAAT/enhancer-binding protein β; PBMC, peripheral blood mononuclear cells; SLE, systemic lupus erythematosus.

Figure 2.

C/EBP β relative mRNA expression in PBMCs from SLE patients with various autoantibodies. (A) The difference in C/EBP β relative mRNA expression between SLE patients with high ANA titer (≤1:160; n=3) and low ANA (≥1:80; n=17) titer was analyzed with a Mann-Whitney test. (B) The difference in C/EBP β relative mRNA expression between patients positive (n=7) and negative (n=13) for anti-Sm antibody, or (C) between patients positive (n=10) and negative (n=10) for anti-nRNP antibody was analyzed with a Mann-Whitney test. SLE, systemic lupus erythematosus; C/EBP β, CCAAT/enhancer-binding protein β; PBMC, peripheral blood mononuclear cells; ANA, anti-nuclear antibody; anti-dsDNA, anti-dsDNA antibody; anti-Sm, anti-Smith antibody; anti-nRNP, anti-nuclear ribonuclear protein.

Figure 3.

Correlation analysis of C/EBP β mRNA expression level with the clinical characteristics of patients with SLE. The association between C/EBP β mRNA expression levels, (A) SLEDAI and complement (B) C3 and (C) C4 was analyzed by Spearman's rank test in the patients with SLE (n=20). SLE, systemic lupus erythematosus; C/EBP β, CCAAT/enhancer-binding protein β; SLEDAI, SLE disease activity index.

Figure 4.

Correlation analysis of C/EBP β mRNA expression levels with TNIP1 and TNFAIP3 expression in patients with SLE. The association between C/EBP β mRNA expression levels and (A) TNIP1 and (B) TNFAIP3 expression was analyzed by Spearman's rank test in patients with SLE (n=20). SLE, systemic lupus erythematosus; C/EBP β, CCAAT/enhancer-binding protein β; TNFAIP3, tumor necrosis factor α-induced protein 3; TNIP1, TNFAIP3-interacting protein 1.