Altered expression of TNFSF4 and TRAF2 mRNAs in peripheral blood mononuclear cells in patients with systemic lupus erythematosus: association with atherosclerotic symptoms and lupus nephritis | springermedicine.com

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Inflammation Research

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01-12-2012 | Original Research Paper

Altered expression of TNFSF4 and TRAF2 mRNAs in peripheral blood mononuclear cells in patients with systemic lupus erythematosus: association with atherosclerotic symptoms and lupus nephritis

Authors: Peyman Rajabi, Mahsa Alaee, Kazem Mousavizadeh, Ali Samadikuchaksaraei

Published in: Inflammation Research | Issue 12/2012

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Abstract

Objectives

This study compares the expression levels of tumor necrosis factor ligand superfamily member 4 (TNFSF4) and TNF-R-associated factor 2 (TRAF2) mRNAs in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE) against healthy controls. The association of SLE disease activity index (SLEDAI) and clinical features of SLE with altered expression levels of TNFSF4 and TRAF2 mRNAs were also evaluated.

Design

We used real-time reverse transcription polymerase chain reaction to measure TNFSF4 and TRAF2 mRNAs expression levels in peripheral blood mononuclear cells of 57 SLE patients and 57 healthy controls.

Results

The expression level of TNFSF4 mRNA was significantly higher in SLE patients than in the control group. Overexpression of TNFSF4 was correlated with arthritis, atherosclerosis and lupus nephritis. TRAF2 mRNA was underexpressed in PBMCs of SLE patients, and its lower expression was associated with atherosclerosis and lupus nephritis. The altered expression levels of TNFSF4 and TRAF2 mRNAs was significantly correlated with SLEDAI.

Conclusion

Our results suggest that changes in the expression levels of TNFSF4 and TRAF2 mRNAs may significantly correlate with the pathogenesis of SLE, the disease activity and different clinical features of lupus, particularly lupus nephritis, atherosclerosis and arthritis.

1.

Rahman A, Isenberg DA. Systemic lupus erythematosus. N Engl J Med. 2008;358:929–39.PubMedCrossRef

2.

Weckerle CE, Franek BS, Kelly JA, Kumabe M, Mikolaitis RA, Green SL, et al. Network analysis of associations between serum interferon-alpha activity, autoantibodies, and clinical features in systemic lupus erythematosus. Arthritis Rheum. 2011;63:1044–53.PubMedCrossRef

3.

Heinlen LD, McClain MT, Merrill J, Akbarali YW, Edgerton CC, Harley JB, et al. Clinical criteria for systemic lupus erythematosus precede diagnosis, and associated autoantibodies are present before clinical symptoms. Arthritis Rheum. 2007;56(7):2344–51.PubMedCrossRef

4.

Niewold TB, Hua J, Lehman TJ, Harley JB, Crow MK. High serum IFN-alpha activity is a heritable risk factor for systemic lupus erythematosus. Genes Immun. 2007;8:492–502.PubMedCrossRef

5.

Sestak AL, Fürnrohr BG, Harley JB, Merrill JT, Namjou B. The genetics of systemic lupus erythematosus and implications for targeted therapy. Ann Rheum Dis. 2011;70(Suppl 1):i37–43.PubMedCrossRef

6.

Harley IT, Kaufman KM, Langefeld CD, Harley JB, Kelly JA. Genetic susceptibility to SLE: new insights from fine mapping and genome-wide association studies. Nat Rev Genet. 2009;10:285–90.PubMedCrossRef

7.

Chang YK, Yang W, Zhao M, Mok CC, Chan TM, Wong RW, et al. Association of BANK1 and TNFSF4 with systemic lupus erythematosus in Hong Kong Chinese. Genes Immun. 2009;10(5):414–20.PubMedCrossRef

8.

Zhang SQ, Han JW, Sun LD, Lu WS, Yin XY, Zhang XJ, et al. A single-nucleotide polymorphism of the TNFSF4 gene is associated with systemic lupus erythematosus in Chinese Han population. Rheumatol Int. 2011;31(2):227–31.PubMedCrossRef

9.

Weinberg AD, Wegmann KW, Funatake C, Whitham RH. Blocking OX-40/OX-40 ligand interaction in vitro and in vivo leads to decreased T cell function and amelioration of experimental allergic encephalomyelitis. J Immunol. 1999;162:1818–26.PubMed

10.

Godfrey WR, Fagnoni FF, Harara MA, Buck D, Engleman EG. Identification of a human OX-40 ligand, a costimulator of CD4+ T cells with homology to tumor necrosis factor. J Exp Med. 1994;180:757–62.PubMedCrossRef

11.

Ito T, Wang YH, Duramad O, Hori T, Delespesse GJ, Watanabe N, et al. TSLP-activated dendritic cells induce an inflammatory T helper type 2 cell response through OX40 ligand. J Exp Med. 2005;202(9):1213–23.PubMedCrossRef

12.

Barrios CS, Johnson BD, Henderson DJ Jr, Fink JN, Kelly KJ, Kurup VP. The costimulatory molecules CD80, CD86 and OX40L are up-regulated in Aspergillus fumigatus sensitized mice. Clin Exp Immunol. 2005;142:242–50.PubMedCrossRef

13.

Ohshima Y, Tanaka Y, Tozawa H, Takahashi Y, Maliszewski C, Delespesse G. Expression and function of OX40 ligand on human dendritic cells. J Immunol. 1997;159:3838–48.PubMed

14.

Lanzavecchia A, Sallusto F. Antigen decoding by T lymphocytes: from synapses to fate determination. Nat Immunol. 2001;2:487–92.PubMedCrossRef

15.

Linton PJ, Bautista B, Bierderman E, Bradley ES, Harbertson J, Kondrack RM, et al. Costimulation via OX40L expressed by B cells is sufficient to determine the extent of primary CD4 cell expansion and Th2 cytokine secretion in vivo. J Exp Med. 2003;197:875–83.PubMedCrossRef

16.

Chan KF, Siegel MR, Lenardo JM. Signaling by the TNF receptor superfamily and T cell homeostasis. Immunity. 2000;13(4):419–22.PubMedCrossRef

17.

Locksley R, Killeen N, Lenardo M. The TNF and TNF receptor superfamilies integrating mammalian biology. Cell. 2001;104:487–501.PubMedCrossRef

18.

Aggarwal BB. Signaling pathways of the TNF superfamily a double-edged sword. Nat Rev Immunol. 2003;3:745–56.PubMedCrossRef

19.

Giuliani C, Napolitano G, Bucci I, Montani V, Monaco F. NF-kB transcription factor: role in the pathogenesis of inflammatory, autoimmune, and neoplastic diseases and therapy implications. Clin Ter. 2001;152(4):249–53.PubMed

20.

Toubi E, Shoenfeld Y. The role of CD 40–CD 154 interactions in autoimmunity and the benefit of disrupting this pathway. Autoimmunity. 2004;37:457–64.PubMedCrossRef

21.

Quezada SA, Eckert M, Adeyi OA, Schned AR, Noelle RJ, Burns CM. Distinct mechanisms of action of anti-CD 154 in early versus late treatment of murine lupus nephritis. Arthritis Rheum. 2003;48:2541–54.PubMedCrossRef

22.

Bradley JR, Pober JS. Tumor necrosis factor receptor-associated factors (TRAFs). Oncogene. 2001;20(44):6482–91.PubMedCrossRef

23.

Hayden MS, West AP, Ghosh S. NF-κB and the immune response. Oncogene. 2006;25(51):6758–80.PubMedCrossRef

24.

Arch RH, Thompson CB. 4–1BB and Ox40 are members of a tumor necrosis factor (TNF)-nerve growth factor receptor subfamily that bind TNF receptor-associated factors and activate nuclear factor kappa B. Mol Cell Biol. 1998;18(1):558–65.PubMed

25.

Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40:1725.PubMedCrossRef

26.

Gladman DD, Ibanez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000. J Rheumatol. 2002;29:288–91.PubMed

27.

Takasawa N, Ishii N, Higashimura N, Murata K, Tanaka Y, Nakamura M, et al. Expression of gp34 (OX40 ligand) and OX40 on human T cell clones. Jpn J Cancer Res. 2001;92:377.PubMedCrossRef

28.

Stüber E, Strober W. The T cell-B cell interaction via OX40-OX40L is necessary for the T cell-dependent humoral immune response. J Exp Med. 1996;183:979.PubMedCrossRef

29.

Murata K, Ishii N, Takano H, Miura S, Ndhlovu LC, Nose M, et al. Impairment of antigen-presenting cell function in mice lacking expression of OX40 ligand. J Exp Med. 2000;191:365.PubMedCrossRef

30.

Imura A, Hori T, Imada K, Ishikawa T, Tanaka Y, Maeda M, et al. The human OX40/gp34 system directly mediates adhesion of activated T cells to vascular endothelial cells. J Exp Med. 1996;183:2185.PubMedCrossRef

31.

Maxwell JR, Weinberg A, Prell RA, Vella AT. Danger and OX40 receptor signaling synergize to enhance memory T cell survival by inhibiting peripheral deletion. J Immunol. 2000;164:107.PubMed

32.

Gramaglia I, Jember A, Pippig SD, Weinberg AD, Killeen N, Croft M. The OX40 costimulatory receptor determines the development of CD4 memory by regulating primary clonal expansion. J Immunol. 2000;165:3043.PubMed

33.

Bansal-Pakala P, Gebre-Hiwot Jember A, Croft M. Signaling through OX40 (CD134) breaks peripheral T-cell tolerance. Nature Med. 2001;7:907–12.PubMedCrossRef

34.

Kato H, Kojima H, Ishii N, Hase H, Imai Y, Fujibayashi T, et al. Essential role of OX40L on B cells in persistent alloantibody production following repeated alloimmunizations. J Clin Immunol. 2004;24(3):237–48.PubMedCrossRef

35.

Ito T, Amakawa R, Inaba M, Hori T, Ota M, Nakamura K, et al. Plasmacytoid dendritic cells regulate Th cell response through OX40 ligand and type I IFNs. J Immunol. 2004;172(7):4253–9.PubMed

36.

Murata K, Nose M, Ndhlovu LC, Sato T, Sugamura K, Ishii N. Constitutive OX40/OX40 ligand interaction induces autoimmune-like diseases. J Immunol. 2002;169(8):4628–36.PubMed

37.

Pakala SV, Bansal-Pakala P, Halteman BS, Croft M. Prevention of diabetes in NOD mice at a late stage by targeting OX40/OX40 ligand interactions. Eur J Immunol. 2004;34(11):3039–46.PubMedCrossRef

38.

Kawamata S, Hori T, Imura A, Takaori-Kondo A, Uchiyama T. Activation of OX40 signal transduction pathways leads to tumor necrosis factor receptor-associated factor (TRAF) 2- and TRAF5-mediated NF-kappaB activation. J Biol Chem. 1998;273(10):5808–14.PubMedCrossRef

39.

Zhou XJ, Lu XL, Nath SK, Lv JC, Zhu SN, Yang HZ, et al. Gene-gene interaction of BLK, TNFSF4, TRAF1, TNFAIP3, and REL in systemic lupus erythematosus. Arthritis Rheum. 2012;64(1):222–31.PubMedCrossRef

40.

Sanchez E, Webb RD, Rasmussen A, Kelly JA, Riba L, Kaufman KM, et al. Genetically determined Amerindian ancestry correlates with increased frequency of risk alleles for systemic lupus erythematosus. Arthritis Rheum. 2010;62(12):3722–9.PubMedCrossRef

41.

Ramos PS, Brown EE, Kimberly RP, Langefeld CD. Genetic factors predisposing to systemic lupus erythematosus and lupus nephritis. Semin Nephrol. 2010;30(2):164–76.PubMedCrossRef

42.

Olofsson PS, Söderström LA, Jern C, Sirsjö A, Ria M, Sundler E, et al. Genetic variants of TNFSF4 and risk for carotid artery disease and stroke. J Mol Med. 2009;87(4):337–46.PubMedCrossRef

43.

Wang X, Ria M, Kelmenson PM, Eriksson P, Higgins DC, Samnegard A, et al. Positional identification of TNFSF4, encoding OX40 ligand, as a gene that influences atherosclerosis susceptibility. Nat Genet. 2005;37:365–72.PubMedCrossRef

44.

Yoshioka T, Nakajima A, Akiba H, Ishiwata T, Asano G, Yoshino S, et al. Contribution of OX40/OX40 ligand interaction to the pathogenesis of rheumatoid arthritis. Eur J Immunol. 2000;30:2815.PubMedCrossRef

45.

Farres MN, Al-Zifzaf DS, Aly AA. Abd Raboh NM. OX40/OX40L in systemic lupus erythematosus: association with disease activity and lupus nephritis. Ann Saudi Med. 2011;31(1):29–34.PubMedCrossRef

46.

Foell J, Strahotin S, O’Neil SP, McCausland MM, Suwyn C, Haber M, et al. CD137 co-stimulatory T cell receptor engagement reverses acute disease in lupus-prone NZB x NZW F1 mice. J Clin Invest. 2003;111:1505–18.PubMed

47.

Aten J, Roos A, Claessen N, Schilder-Tol EJ, ten Berge IJ, Weening JJ. Strong and selective glomerular localization of CD134 ligand and TNF receptor-1 in proliferative lupus nephritis. J Am Soc Nephrol. 2000;11:1426–38.PubMed

48.

Xie P, Hostager BS, Munroe ME, Moore CR, Bishop GA. Cooperation between TNF receptor-associated factors 1 and 2 in CD40 signaling. J Immunol. 2006;176:5388–400.PubMed

49.

Baud V, Karin M. Signal transduction by tumor necrosis factor and its relatives. Trends Cell Biol. 2001;9(11):372–7.CrossRef

50.

Van Antwerp DJ, Martin SJ, Kafri T, Green DR, Verma IM. Suppression of TNF-alpha-induced apoptosis by NF-kappa B. Science. 1996;274(5288):787–9.PubMedCrossRef

51.

Beg AA, Baltimore D. An essential role for NF-kappaB in preventing TNF-alpha-induced cell death. Science. 1996;274(5288):782–4.PubMedCrossRef

52.

Maas K, Chan S, Parker J, Slater A, Moore J, Olsen N, et al. Cutting edge: molecular portrait of human autoimmune disease. J Immunol. 2002;169:5–9.PubMed

53.

Gordon C, Salmon M. Update on systemic lupus erythematosus: autoantibodies and apoptosis. Clin Med. 2001;1:10–4.PubMed

Title: Altered expression of TNFSF4 and TRAF2 mRNAs in peripheral blood mononuclear cells in patients with systemic lupus erythematosus: association with atherosclerotic symptoms and lupus nephritis
Authors: Peyman Rajabi
Mahsa Alaee
Kazem Mousavizadeh
Ali Samadikuchaksaraei
Publication date: 01-12-2012
Publisher: SP Birkhäuser Verlag Basel
Published in: Inflammation Research / Issue 12/2012
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI: https://doi.org/10.1007/s00011-012-0535-6

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