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

Qian,Tian; Chen,Yan; Shi,Xiaowei; Li,Jian; Hao,Fei; Zhang,Dongmei

doi:10.3892/etm.2016.3612

October-2016 Volume 12 Issue 4

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October-2016 Volume 12 Issue 4

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Article

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

Authors:
- Tian Qian
- Yan Chen
- Xiaowei Shi
- Jian Li
- Fei Hao
- Dongmei Zhang
View Affiliations / Copyright

Affiliations: Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China
Pages: 2348-2354
|
Published online on: August 23, 2016

https://doi.org/10.3892/etm.2016.3612
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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.

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1	Yanaba K, Bouaziz JD, Matsushita T, Magro CM, St Clair EW and Tedder TF: B-lymphocyte contributions to human autoimmune disease. Immunol Rev. 223:284–299. 2008. View Article : Google Scholar : PubMed/NCBI
2	Mak A and Kow N: The pathology of T cells in systemic lupus erythematosus. J Immunol Res. 2014:4190292014. View Article : Google Scholar : PubMed/NCBI
3	Celhar T, Magalhães R and Fairhurst AM: TLR7 and TLR9 in SLE: When sensing self goes wrong. Immunol Res. 53:58–77. 2012. View Article : Google Scholar : PubMed/NCBI
4	Kunz M: Lupus erythematosus. Part I: Epidemiology, genetics and immunology. J Dtsch Dermatol Ges. 11:709–719; quiz 720, 709–720; quiz 721. 2013.[(In English, German)]. View Article : Google Scholar : PubMed/NCBI
5	Davis LS, Hutcheson J and Mohan C: The role of cytokines in the pathogenesis and treatment of systemic lupus erythematosus. J Interferon Cytokine Res. 31:781–789. 2011. View Article : Google Scholar : PubMed/NCBI
6	Ramji DP and Foka P: CCAAT/enhancer-binding proteins: Structure, function and regulation. Biochem J. 365:561–575. 2002. View Article : Google Scholar : PubMed/NCBI
7	Sears RC and Sealy L: Multiple forms of C/EBP beta bind the EFII enhancer sequence in the Rous sarcoma virus long terminal repeat. Mol Cell Biol. 14:4855–4871. 1994. View Article : Google Scholar : PubMed/NCBI
8	Yamanaka R, Lekstrom-Himes J, Barlow C, Wynshaw-Boris A and Xanthopoulos KG: CCAAT/enhancer binding proteins are critical components of the transcriptional regulation of hematopoiesis (Review). Int J Mol Med. 1:213–221. 1998.PubMed/NCBI
9	Li-Weber M, Salgame P, Hu C, Davydov IV and Krammer PH: Differential interaction of nuclear factors with the PRE-I enhancer element of the human IL-4 promoter in different T cell subsets. J Immunol. 158:1194–1200. 1997.PubMed/NCBI
10	Huber R, Pietsch D, Panterodt T and Brand K: Regulation of C/EBPβ and resulting functions in cells of the monocytic lineage. Cell Signal. 24:1287–1296. 2012. View Article : Google Scholar : PubMed/NCBI
11	Lane MD, Tang QQ and Jiang MS: Role of the CCAAT enhancer binding proteins (C/EBPs) in adipocyte differentiation. Biochem Biophys Res Commun. 266:677–683. 1999. View Article : Google Scholar : PubMed/NCBI
12	Zahnow CA: CCAAT/enhancer-binding protein beta: Its role in breast cancer and associations with receptor tyrosine kinases. Expert Rev Mol Med. 11:e122009. View Article : Google Scholar : PubMed/NCBI
13	Fausto N: Liver regeneration. J Hepatol. 32(1): Suppl. S19–S31. 2000. View Article : Google Scholar
14	Tengku-Muhammad TS, Hughes TR, Ranki H, Cryer A and Ramji DP: Differential regulation of macrophage CCAAT-enhancer binding protein isoforms by lipopolysaccharide and cytokines. Cytokine. 12:1430–1436. 2000. View Article : Google Scholar : PubMed/NCBI
15	Natsuka S, Akira S, Nishio Y, Hashimoto S, Sugita T, Isshiki H and Kishimoto T: Macrophage differentiation-specific expression of NF-IL6, a transcription factor for interleukin-6. Blood. 79:460–466. 1992.PubMed/NCBI
16	Nolan A, Weiden MD, Thurston G and Gold JA: Vascular endothelial growth factor blockade reduces plasma cytokines in a murine model of polymicrobial sepsis. Inflammation. 28:271–278. 2004. View Article : Google Scholar : PubMed/NCBI
17	Peng H, Wang W, Zhou M, Li R, Pan HF and Ye DQ: Role of interleukin-10 and interleukin-10 receptor in systemic lupus erythematosus. Clin Rheumatol. 32:1255–1266. 2013. View Article : Google Scholar : PubMed/NCBI
18	Yap DY and Lai KN: The role of cytokines in the pathogenesis of systemic lupus erythematosus-from bench to bedside. Nephrology (Carlton). 18:243–255. 2013. View Article : Google Scholar : PubMed/NCBI
19	Fojtíková M, Cerná M and Pavelka K: A review of the effects of prolactin hormone and cytokine on the development and pathogenesis of autoimmune diseases. Vnitr Lek. 56:402–413. 2010.(In Czech). PubMed/NCBI
20	Cigni A, Pileri PV, Faedda R, Gallo P, Sini A, Satta AE, Marras R, Carta E, Argiolas D, Rum I and Masala A: Interleukin 1, interleukin 6, interleukin 10, and tumor Necrosis factor α in active and quiescent systemic lupus erythematosus. J Investig Med. 62:825–829. 2014. View Article : Google Scholar : PubMed/NCBI
21	Lyn-Cook BD, Xie C, Oates J, Treadwell E, Word B, Hammons G and Wiley K: Increased expression of Toll-like receptors (TLRs) 7 and 9 and other cytokines in systemic lupus erythematosus (SLE) patients: Ethnic differences and potential new targets for therapeutic drugs. Mol Immunol. 61:38–43. 2014. View Article : Google Scholar : PubMed/NCBI
22	Zhou L, Lu G, Shen L, Wang L and Wang M: Serum levels of three angiogenic factors in systemic lupus erythematosus and their clinical significance. Biomed Res Int. 2014:6271262014. View Article : Google Scholar : PubMed/NCBI
23	Ma A and Malynn BA: A20: Linking a complex regulator of ubiquitylation to immunity and human disease. Nat Rev Immunol. 12:774–785. 2012. View Article : Google Scholar : PubMed/NCBI
24	Lai TY, Wu SD, Tsai MH, Chuang EY, Chuang LL, Hsu LC and Lai LC: Transcription of Tnfaip3 is regulated by NF-κB and p38 via C/EBPβ in activated macrophages. PLoS One. 8:e731532013. View Article : Google Scholar : PubMed/NCBI
25	Gateva V, Sandling JK, Hom G, Taylor KE, Chung SA, Sun X, Ortmann W, Kosoy R, Ferreira RC, Nordmark G, et al: A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus. Nat Genet. 41:1228–1233. 2009. View Article : Google Scholar : PubMed/NCBI
26	Zhou J, Wu R, High AA, Slaughter CA, Finkelstein D, Rehg JE, Redecke V and Häcker H: A20-binding inhibitor of NF-κB (ABIN1) controls Toll-like receptor-mediated CCAAT/enhancer-binding protein β activation and protects from inflammatory disease. Proc Natl Acad Sci USA. 108:E998–E1006. 2011. View Article : Google Scholar : PubMed/NCBI
27	Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N and Winchester RJ: The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 25:1271–1277. 1982. View Article : Google Scholar : PubMed/NCBI
28	Gladman DD, Ibanez D and Urowitz MB: Systemic lupus erythematosus disease activity index 2000. J Rheumatol. 29:288–291. 2002.PubMed/NCBI
29	Wrone DA and Kwon NJ: Andrews' diseases of the skin: Clinical dermatology. Archives of Dermatology. 137:518. 2001.
30	O'Neill LA, Bryant CE and Doyle SL: Therapeutic targeting of Toll-like receptors for infectious and inflammatory diseases and cancer. Pharmacol Rev. 61:177–197. 2009. View Article : Google Scholar : PubMed/NCBI
31	Kawai T, Adachi O, Ogawa T, Takeda K and Akira S: Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity. 11:115–122. 1999. View Article : Google Scholar : PubMed/NCBI
32	Häcker H, Vabulas RM, Takeuchi O, Hoshino K, Akira S and Wagner H: Immune cell activation by bacterial CpG-DNA through myeloid differentiation marker 88 and tumor necrosis factor receptor-associated factor (TRAF)6. J Exp Med. 192:595–600. 2000. View Article : Google Scholar : PubMed/NCBI
33	Häcker H, Redecke V, Blagoev B, Kratchmarova I, Hsu LC, Wang GG, Kamps MP, Raz E, Wagner H, Häcker G, et al: Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6. Nature. 439:204–207. 2006. View Article : Google Scholar : PubMed/NCBI
34	Horie R, Ishida T, Maruyama-Nagai M, Ito K, Watanabe M, Yoneyama A, Higashihara M, Kimura S and Watanabe T: TRAF activation of C/EBPbeta (NF-IL6) via p38 MAPK induces HIV-1 gene expression in monocytes/macrophages. Microbes Infect. 9:721–728. 2007. View Article : Google Scholar : PubMed/NCBI
35	Takeuchi O and Akira S: Pattern recognition receptors and inflammation. Cell. 140:805–820. 2010. View Article : Google Scholar : PubMed/NCBI
36	Han JW, Zheng HF, Cui Y, Sun LD, Ye DQ, Hu Z, Xu JH, Cai ZM, Huang W, Zhao GP, et al: Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus. Nat Genet. 41:1234–1237. 2009. View Article : Google Scholar : PubMed/NCBI
37	Düwel M, Welteke V, Oeckinghaus A, Baens M, Kloo B, Ferch U, Darnay BG, Ruland J, Marynen P and Krappmann D: A20 negatively regulates T cell receptor signaling to NF-kappaB by cleaving Malt1 ubiquitin chains. J Immunol. 182:7718–7728. 2009. View Article : Google Scholar : PubMed/NCBI
38	Li D, Wang L, Fan Y, Song L, Guo C, Zhu F, Zhang L and Shi Y: Down-regulation of A20 mRNA expression in peripheral blood mononuclear cells from patients with systemic lupus erythematosus. J Clin Immunol. 32:1287–1291. 2012. View Article : Google Scholar : PubMed/NCBI
39	Zhang DM, Cheng LQ, Zhai ZF, Feng L, Zhong BY, You Y, Zhang N, Song ZQ, Yang XC, Chen FR and Hao F: Single-nucleotide polymorphism and haplotypes of TNIP1 associated with systemic lupus erythematosus in a Chinese Han population. J Rheumatol. 40:1535–1544. 2013. View Article : Google Scholar : PubMed/NCBI
40	Mele A, Cervantes JR, Chien V, Friedman D and Ferran C: Single nucleotide polymorphisms at the TNFAIP3/A20 locus and susceptibility/resistance to inflammatory and autoimmune diseases. Adv Exp Med Biol. 809:163–183. 2014. View Article : Google Scholar : PubMed/NCBI
41	Musone SL, Taylor KE, Lu TT, Nititham J, Ferreira RC, Ortmann W, Shifrin N, Petri MA, Kamboh MI, Manzi S, et al: Multiple polymorphisms in the TNFAIP3 region are independently associated with systemic lupus erythematosus. Nat Genet. 40:1062–1064. 2008. View Article : Google Scholar : PubMed/NCBI
42	Yildirim-Toruner C and Diamond B: Current and novel therapeutics in the treatment of systemic lupus erythematosus. J Allergy Clin Immunol. 127:303–312; quiz 313–314. 2011. View Article : Google Scholar : PubMed/NCBI
43	Sriskantharajah S and Ley SC: Cell biology. Turning off inflammation signaling. Science. 327:1093–1094. 2010. View Article : Google Scholar : PubMed/NCBI
44	Aringer M and Smolen JS: TNF inhibition in SLE: Where do we stand? Lupus. 18:5–8. 2009. View Article : Google Scholar : PubMed/NCBI