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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 1/2014

Open Access 01-02-2014 | Research article

Elevated signal transducers and activators of transcription 1 correlates with increased C-C motif chemokine ligand 2 and C-X-C motif chemokine 10 levels in peripheral blood of patients with systemic lupus erythematosus

Authors: Paul R Dominguez-Gutierrez, Angela Ceribelli, Minoru Satoh, Eric S Sobel, Westley H Reeves, Edward KL Chan

Published in: Arthritis Research & Therapy | Issue 1/2014

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Abstract

Introduction

The present study examines the levels of recently reported biomarkers, adenosine deaminase acting on RNA (ADAR), C-C motif chemokine ligand 2 (CCL2), C-X-C motif chemokine 10 (CXCL10), signal transducers and activators of transcription 1 (STAT1), and miR-146a in systemic lupus erythematosus (SLE) patients over multiple visits.

Methods

Peripheral blood leukocytes were collected from 65 healthy donors and 103 SLE patients, 60 of whom had samples from 2 or more visits. Total RNA was isolated and analyzed for the expression of mRNA and microRNA using Taqman real time PCR assays. Relative expression of I-IFN signature genes, chemokines, and miR-146a were determined by the ΔΔCT method. Results were correlated with clinical data and analyzed by Wilcoxon/Kruskal-Wallis test and Fisher’s exact test.

Results

Levels of ADAR, CCL2, CXCL10, and STAT1 in SLE were significantly elevated compared with the healthy controls (P <0.0001). ADAR, CCL2, and CXCL10 showed significant correlation with IFN score in both healthy donors (P <0.0033) and SLE patients (P <0.0001). In SLE patients, miR-146a level was not significantly different from healthy controls nor correlated to the IFN score. Two STAT1 populations were identified: a low STAT1 and a high STAT1 group. High STAT1 patient visits displayed higher (P ≤0.0020) levels of CCL2 and CXCL10 than the low STAT1 patient visits. STAT1 levels correlated with IFN score in low STAT1 group but not in high STAT1 group. More importantly, high STAT1 levels appeared as an enhancer of CCL2 and CXCL10 as indicated by the significantly stronger correlation of CCL2 and CXCL10 with IFN score in high STAT1 patient visits relative to low STAT1 patient visits.

Conclusion

Our data indicate a novel role for STAT1 in the pathogenesis of SLE as an expression enhancer of CCL2 and CXCL10 in SLE patients with high levels of STAT1. Future study is needed to examine the exact role of STAT1 in the etiology of SLE.
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Literature
1.
Baechler EC, Batliwalla FM, Karypis G, Gaffney PM, Ortmann WA, Espe KJ, Shark KB, Grande WJ, Hughes KM, Kapur V, Gregersen PK, Behrens TW: Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci USA. 2003, 100: 2610-2615.CrossRefPubMedPubMedCentral
2.
Bennett L, Palucka AK, Arce E, Cantrell V, Borvak J, Banchereau J, Pascual V: Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. J Exp Med. 2003, 197: 711-723.CrossRefPubMedPubMedCentral
3.
Crow MK: Interferon pathway activation in systemic lupus erythematosus. Curr Rheumatol Rep. 2005, 7: 463-468.CrossRefPubMed
4.
Preble OT, Black RJ, Friedman RM, Klippel JH, Vilcek J: Systemic lupus erythematosus: presence in human serum of an unusual acid-labile leukocyte interferon. Science. 1982, 216: 429-431.CrossRefPubMed
5.
Nikpour M, Dempsey AA, Urowitz MB, Gladman DD, Barnes DA: Association of a gene expression profile from whole blood with disease activity in systemic lupus erythaematosus. Ann Rheum Dis. 2008, 67: 1069-1075.CrossRefPubMed
6.
Crow MK, Kirou KA, Wohlgemuth J: Microarray analysis of interferon-regulated genes in SLE. Autoimmunity. 2003, 36: 481-490.CrossRefPubMed
7.
Kirou KA, Lee C, George S, Louca K, Papagiannis IG, Peterson MG, Ly N, Woodward RN, Fry KE, Lau AY, Prentice JG, Wohlgemuth JG, Crow MK: Coordinate overexpression of interferon-alpha-induced genes in systemic lupus erythematosus. Arthritis Rheum. 2004, 50: 3958-3967.CrossRefPubMed
8.
Bass BL, Weintraub H: An unwinding activity that covalently modifies its double-stranded RNA substrate. Cell. 1988, 55: 1089-1098.CrossRefPubMed
9.
Wagner RW, Smith JE, Cooperman BS, Nishikura K: A double-stranded RNA unwinding activity introduces structural alterations by means of adenosine to inosine conversions in mammalian cells and Xenopus eggs. Proc Natl Acad Sci USA. 1989, 86: 2647-2651.CrossRefPubMedPubMedCentral
10.
11.
George CX, Gan Z, Liu Y, Samuel CE: Adenosine deaminases acting on RNA, RNA editing, and interferon action. J Interferon Cytokine Res. 2011, 31: 99-117.CrossRefPubMedPubMedCentral
12.
13.
Toth AM, Li Z, Cattaneo R, Samuel CE: RNA-specific adenosine deaminase ADAR1 suppresses measles virus-induced apoptosis and activation of protein kinase PKR. J Biol Chem. 2009, 284: 29350-29356.CrossRefPubMedPubMedCentral
14.
Li Z, Wolff KC, Samuel CE: RNA adenosine deaminase ADAR1 deficiency leads to increased activation of protein kinase PKR and reduced vesicular stomatitis virus growth following interferon treatment. Virology. 2010, 396: 316-322.CrossRefPubMedPubMedCentral
15.
Laxminarayana D, Khan IU, Kammer G: Transcript mutations of the alpha regulatory subunit of protein kinase A and up-regulation of the RNA-editing gene transcript in lupus T lymphocytes. Lancet. 2002, 360: 842-849.CrossRefPubMed
16.
Laxminarayana D, O’Rourke KS, Maas S, Olorenshaw I: Altered editing in RNA editing adenosine deaminase ADAR2 gene transcripts of systemic lupus erythematosus T lymphocytes. Immunology. 2007, 121: 359-369.CrossRefPubMedPubMedCentral
17.
Orlowski RJ, O’Rourke KS, Olorenshaw I, Hawkins GA, Maas S, Laxminarayana D: Altered editing in cyclic nucleotide phosphodiesterase 8A1 gene transcripts of systemic lupus erythematosus T lymphocytes. Immunology. 2008, 125: 408-419.CrossRefPubMedPubMedCentral
18.
Karonitsch T, Feierl E, Steiner CW, Dalwigk K, Korb A, Binder N, Rapp A, Steiner G, Scheinecker C, Smolen J, Aringer M: Activation of the interferon-gamma signaling pathway in systemic lupus erythematosus peripheral blood mononuclear cells. Arthritis Rheum. 2009, 60: 1463-1471.CrossRefPubMed
19.
Usacheva A, Smith R, Minshall R, Baida G, Seng S, Croze E, Colamonici O: The WD motif-containing protein receptor for activated protein kinase C (RACK1) is required for recruitment and activation of signal transducer and activator of transcription 1 through the type I interferon receptor. J Biol Chem. 2001, 276: 22948-22953.CrossRefPubMed
20.
Ivashkiv LB: Type I interferon modulation of cellular responses to cytokines and infectious pathogens: potential role in SLE pathogenesis. Autoimmunity. 2003, 36: 473-479.CrossRefPubMed
21.
Bauer JW, Baechler EC, Petri M, Batliwalla FM, Crawford D, Ortmann WA, Espe KJ, Li W, Patel DD, Gregersen PK, Behrens TW: Elevated serum levels of interferon-regulated chemokines are biomarkers for active human systemic lupus erythematosus. PLoS Med. 2006, 3: e491-CrossRefPubMedPubMedCentral
22.
Bauer JW, Petri M, Batliwalla FM, Koeuth T, Wilson J, Slattery C, Panoskaltsis-Mortari A, Gregersen PK, Behrens TW, Baechler EC: Interferon-regulated chemokines as biomarkers of systemic lupus erythematosus disease activity: a validation study. Arthritis Rheum. 2009, 60: 3098-3107.CrossRefPubMedPubMedCentral
23.
Yadav A, Saini V, Arora S: MCP-1: chemoattractant with a role beyond immunity: a review. Clin Chim Acta. 2010, 411: 1570-1579.CrossRefPubMed
24.
La Gruta NL, Kedzierska K, Stambas J, Doherty PC: A question of self-preservation: immunopathology in influenza virus infection. Immunol Cell Biol. 2007, 85: 85-92.CrossRefPubMed
25.
Marsche G, Semlitsch M, Hammer A, Frank S, Weigle B, Demling N, Schmidt K, Windischhofer W, Waeg G, Sattler W, Malle E: Hypochlorite-modified albumin colocalizes with RAGE in the artery wall and promotes MCP-1 expression via the RAGE-Erk1/2 MAP-kinase pathway. FASEB J. 2007, 21: 1145-1152.CrossRefPubMed
26.
Lloyd CM, Minto AW, Dorf ME, Proudfoot A, Wells TN, Salant DJ, Gutierrez-Ramos JC: RANTES and monocyte chemoattractant protein-1 (MCP-1) play an important role in the inflammatory phase of crescentic nephritis, but only MCP-1 is involved in crescent formation and interstitial fibrosis. J Exp Med. 1997, 185: 1371-1380.CrossRefPubMedPubMedCentral
27.
Kulkarni O, Pawar RD, Purschke W, Eulberg D, Selve N, Buchner K, Ninichuk V, Segerer S, Vielhauer V, Klussmann S, Anders HJ: Spiegelmer inhibition of CCL2/MCP-1 ameliorates lupus nephritis in MRL-(Fas)lpr mice. J Am Soc Nephrol. 2007, 18: 2350-2358.CrossRefPubMed
28.
Dufour JH, Dziejman M, Liu MT, Leung JH, Lane TE, Luster AD: IFN-gamma-inducible protein 10 (IP-10; CXCL10)-deficient mice reveal a role for IP-10 in effector T cell generation and trafficking. J Immunol. 2002, 168: 3195-3204.CrossRefPubMed
29.
Luster AD, Jhanwar SC, Chaganti RS, Kersey JH, Ravetch JV: Interferon-inducible gene maps to a chromosomal band associated with a (4;11) translocation in acute leukemia cells. Proc Natl Acad Sci USA. 1987, 84: 2868-2871.CrossRefPubMedPubMedCentral
30.
Loetscher M, Loetscher P, Brass N, Meese E, Moser B: Lymphocyte-specific chemokine receptor CXCR3: regulation, chemokine binding and gene localization. Eur J Immunol. 1998, 28: 3696-3705.CrossRefPubMed
31.
Weng Y, Siciliano SJ, Waldburger KE, Sirotina-Meisher A, Staruch MJ, Daugherty BL, Gould SL, Springer MS, DeMartino JA: Binding and functional properties of recombinant and endogenous CXCR3 chemokine receptors. J Biol Chem. 1998, 273: 18288-18291.CrossRefPubMed
32.
Han C, Fu J, Liu Z, Huang H, Luo L, Yin Z: Dipyrithione inhibits IFN-gamma-induced JAK/STAT1 signaling pathway activation and IP-10/CXCL10 expression in RAW264.7 cells. Inflamm Res. 2010, 59: 809-816.CrossRefPubMed
33.
Romagnani P, Crescioli C: CXCL10: a candidate biomarker in transplantation. Clin Chim Acta. 2012, 413: 1364-1373.CrossRefPubMed
34.
Liu M, Guo S, Hibbert JM, Jain V, Singh N, Wilson NO, Stiles JK: CXCL10/IP-10 in infectious diseases pathogenesis and potential therapeutic implications. Cytokine Growth Factor Rev. 2011, 22: 121-130.PubMedPubMedCentral
35.
36.
Taganov KD, Boldin MP, Chang KJ, Baltimore D: NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci USA. 2006, 103: 12481-12486.CrossRefPubMedPubMedCentral
37.
Nahid MA, Rivera M, Lucas A, Chan EK, Kesavalu L: Polymicrobial infection with periodontal pathogens specifically enhances microRNA miR-146a in ApoE−/− mice during experimental periodontal disease. Infect Immun. 2011, 79: 1597-1605.CrossRefPubMedPubMedCentral
38.
Nahid MA, Satoh M, Chan EKL: Mechanistic role of microRNA-146a in endotoxin-induced differential cross-regulation of TLR signaling. J Immunol. 2011, 186: 1723-1734.CrossRefPubMedPubMedCentral
39.
Nahid MA, Pauley KM, Satoh M, Chan EKL: miR-146a is critical for endotoxin-induced tolerance: Implication in innate immunity. J Biol Chem. 2009, 284: 34590-34599.CrossRefPubMedPubMedCentral
40.
Pauley KM, Stewart CM, Gauna AE, Dupre LC, Kuklani R, Chan AL, Pauley BA, Reeves WH, Chan EK, Cha S: Altered miR-146a expression in Sjogren’s syndrome and its functional role in innate immunity. Eur J Immunol. 2011, 41: 2029-2039.CrossRefPubMedPubMedCentral
41.
Sonkoly E, Stahle M, Pivarcsi A: MicroRNAs: novel regulators in skin inflammation. Clin Exp Dermatol. 2008, 33: 312-315.CrossRefPubMed
42.
Sonkoly E, Wei T, Janson PC, Saaf A, Lundeberg L, Tengvall-Linder M, Norstedt G, Alenius H, Homey B, Scheynius A, Stahle M, Pivarcsi A: MicroRNAs: novel regulators involved in the pathogenesis of psoriasis?. PLoS One. 2007, 2: e610-CrossRefPubMedPubMedCentral
43.
Nakasa T, Miyaki S, Okubo A, Hashimoto M, Nishida K, Ochi M, Asahara H: Expression of microRNA-146 in rheumatoid arthritis synovial tissue. Arthritis Rheum. 2008, 58: 1284-1292.CrossRefPubMedPubMedCentral
44.
Pauley KM, Satoh M, Chan AL, Bubb MR, Reeves WH, Chan EKL: Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients. Arthritis Res Ther. 2008, 10: R101-CrossRefPubMedPubMedCentral
45.
Stanczyk J, Pedrioli DM, Brentano F, Sanchez-Pernaute O, Kolling C, Gay RE, Detmar M, Gay S, Kyburz D: Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis. Arthritis Rheum. 2008, 58: 1001-1009.CrossRefPubMed
46.
Tang Y, Luo X, Cui H, Ni X, Yuan M, Guo Y, Huang X, Zhou H, de Vries N, Tak PP, Chen S, Shen N: MicroRNA-146A contributes to abnormal activation of the type I interferon pathway in human lupus by targeting the key signaling proteins. Arthritis Rheum. 2009, 60: 1065-1075.CrossRefPubMed
47.
Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ: The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982, 25: 1271-1277.CrossRefPubMed
48.
Yamasaki Y, Narain S, Hernandez L, Barker T, Ikeda K, Segal MS, Richards HB, Chan EK, Reeves WH, Satoh M: Autoantibodies against the replication protein A complex in systemic lupus erythematosus and other autoimmune diseases. Arthritis Res Ther. 2006, 8: R111-CrossRefPubMedPubMedCentral
49.
Feng X, Wu H, Grossman JM, Hanvivadhanakul P, FitzGerald JD, Park GS, Dong X, Chen W, Kim MH, Weng HH, Furst DE, Gorn A, McMahon M, Taylor M, Brahn E, Hahn BH, Tsao BP: Association of increased interferon-inducible gene expression with disease activity and lupus nephritis in patients with systemic lupus erythematosus. Arthritis Rheum. 2006, 54: 2951-2962.CrossRefPubMed
50.
Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH: Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum. 1992, 35: 630-640.CrossRefPubMed
51.
Touma Z, Gladman DD, Urowitz MB: Cinical Meausres, Metrics, and indices. Dubois’ Lupus Erythematosus and Related Syndromes. Edited by: Wallace D, Hahn BH. 2012, Philadelphia, PA: Elsevier Health Sciences, 563-581. 8th edition.
52.
Nahid MA, Yao B, Dominguez-Gutierrez PR, Kesavalu L, Satoh M, Chan EKL: Regulation of TLR2-Mediated Tolerance and Cross-Tolerance through IRAK4 Modulation by miR-132 and miR-212. J Immunol. 2013, 190: 1250-1263.CrossRefPubMedPubMedCentral
53.
Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 2001, 25: 402-408.CrossRefPubMed
54.
Hanley JA, Negassa A, Edwardes MD, Forrester JE: Statistical analysis of correlated data using generalized estimating equations: an orientation. Am J Epidemiol. 2003, 157: 364-375.CrossRefPubMed
55.
Ho A, Magder LS, Barr SG, Petri M: Decreases in anti-double-stranded DNA levels are associated with concurrent flares in patients with systemic lupus erythematosus. Arthritis Rheum. 2001, 44: 2342-2349.CrossRefPubMed
56.
Bootsma H, Spronk P, Derksen R, de Boer G, Wolters-Dicke H, Hermans J, Limburg P, Gmelig-Meyling F, Kater L, Kallenberg C: Prevention of relapses in systemic lupus erythematosus. Lancet. 1995, 345: 1595-1599.CrossRefPubMed
57.
ter Borg EJ, Horst G, Hummel EJ, Limburg PC, Kallenberg CG: Measurement of increases in anti-double-stranded DNA antibody levels as a predictor of disease exacerbation in systemic lupus erythematosus. A long-term, prospective study. Arthritis Rheum. 1990, 33: 634-643.CrossRefPubMed
58.
Isenberg DA, Garton M, Reichlin MW, Reichlin M: Long-term follow-up of autoantibody profiles in black female lupus patients and clinical comparison with Caucasian and Asian patients. Br J Rheumatol. 1997, 36: 229-233.CrossRefPubMed
59.
Bengtsson AA, Sturfelt G, Truedsson L, Blomberg J, Alm G, Vallin H, Ronnblom L: Activation of type I interferon system in systemic lupus erythematosus correlates with disease activity but not with antiretroviral antibodies. Lupus. 2000, 9: 664-671.CrossRefPubMed
60.
Ching KH, Burbelo PD, Tipton C, Wei C, Petri M, Sanz I, Iadarola MJ: Two major autoantibody clusters in systemic lupus erythematosus. PLoS One. 2012, 7: e32001-CrossRefPubMedPubMedCentral
61.
To CH, Petri M: Is antibody clustering predictive of clinical subsets and damage in systemic lupus erythematosus?. Arthritis Rheum. 2005, 52: 4003-4010.CrossRefPubMed
62.
Umareddy I, Tang KF, Vasudevan SG, Devi S, Hibberd ML, Gu F: Dengue virus regulates type I interferon signalling in a strain-dependent manner in human cell lines. J Gen Virol. 2008, 89: 3052-3062.CrossRefPubMed
63.
Perry ST, Buck MD, Lada SM, Schindler C, Shresta S: STAT2 mediates innate immunity to Dengue virus in the absence of STAT1 via the type I interferon receptor. PLoS Pathog. 2011, 7: e1001297-CrossRefPubMedPubMedCentral
64.
Walker GA, Shostak J: Common statistical methods for clinical research with SAS examples. 2010, Cary, NC: SAS Institute Inc., 3rd edition.
65.
66.
Qing X, Putterman C: Gene expression profiling in the study of the pathogenesis of systemic lupus erythematosus. Autoimmun Rev. 2004, 3: 505-509.CrossRefPubMed
67.
Luo X, Yang W, Ye DQ, Cui H, Zhang Y, Hirankarn N, Qian X, Tang Y, Lau YL, de Vries N, Tak PP, Tsao BP, Shen N: A functional variant in MicroRNA-146a promoter modulates its expression and confers disease risk for systemic lupus erythematosus. PLoS Genet. 2011, 7: e1002128-CrossRefPubMedPubMedCentral
68.
George CX, Das S, Samuel CE: Organization of the mouse RNA-specific adenosine deaminase Adar1 gene 5′-region and demonstration of STAT1-independent, STAT2-dependent transcriptional activation by interferon. Virology. 2008, 380: 338-343.CrossRefPubMedPubMedCentral
69.
Tassiulas I, Hu X, Ho H, Kashyap Y, Paik P, Hu Y, Lowell CA, Ivashkiv LB: Amplification of IFN-alpha-induced STAT1 activation and inflammatory function by Syk and ITAM-containing adaptors. Nat Immunol. 2004, 5: 1181-1189.CrossRefPubMed
70.
Hu X, Herrero C, Li WP, Antoniv TT, Falck-Pedersen E, Koch AE, Woods JM, Haines GK, Ivashkiv LB: Sensitization of IFN-gamma Jak-STAT signaling during macrophage activation. Nat Immunol. 2002, 3: 859-866.CrossRefPubMed
71.
Fulkerson PC, Zimmermann N, Hassman LM, Finkelman FD, Rothenberg ME: Pulmonary chemokine expression is coordinately regulated by STAT1, STAT6, and IFN-gamma. J Immunol. 2004, 173: 7565-7574.CrossRefPubMed
72.
Kok SH, Hong CY, Kuo MY, Wang CC, Hou KL, Lin YT, Galson DL, Lin SK: Oncostatin M-induced CCL2 transcription in osteoblastic cells is mediated by multiple levels of STAT-1 and STAT-3 signaling: an implication for the pathogenesis of arthritis. Arthritis Rheum. 2009, 60: 1451-1462.CrossRefPubMed
73.
Valente AJ, Xie JF, Abramova MA, Wenzel UO, Abboud HE, Graves DT: A complex element regulates IFN-gamma-stimulated monocyte chemoattractant protein-1 gene transcription. J Immunol. 1998, 161: 3719-3728.PubMed
Metadata
Title
Elevated signal transducers and activators of transcription 1 correlates with increased C-C motif chemokine ligand 2 and C-X-C motif chemokine 10 levels in peripheral blood of patients with systemic lupus erythematosus
Authors
Paul R Dominguez-Gutierrez
Angela Ceribelli
Minoru Satoh
Eric S Sobel
Westley H Reeves
Edward KL Chan
Publication date
01-02-2014
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2014
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar4448

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