Increased expression of microRNA-155 in peripheral blood mononuclear cells from psoriasis patients is related to disease activity

被引:38
作者
Garcia-Rodriguez, S. [1 ]
Arias-Santiago, S. [2 ]
Blasco-Morente, G. [2 ]
Orgaz-Molina, J. [2 ]
Rosal-Vela, A. [1 ]
Navarro, P. [1 ]
Magro-Checa, C. [3 ,4 ]
Martinez-Lopez, A. [2 ]
Ruiz, J. -C. [2 ]
Raya, E. [3 ]
Naranjo-Sintes, R. [2 ]
Sancho, J. [1 ]
Zubiaur, M. [1 ]
机构
[1] CSIC, IPBLN, Dept Cellular Biol & Immunol, PTS Granada,Av Conocimiento 17, Granada 18016, Spain
[2] Univ Granada UGR, HU Granada, Ibs GRANADA, Inst Invest Biosanitaria Granada,Dept Dermatol, Granada, Spain
[3] Univ Granada UGR, HU Granada, Ibs GRANADA, Inst Invest Biosanitaria Granada,Dept Rheumatol, Granada, Spain
[4] Leiden Univ, Dept Rheumatol, Med Ctr, Leiden, Netherlands
关键词
RHEUMATOID-ARTHRITIS PATIENTS; INNATE IMMUNE-RESPONSE; CYTOKINE SIGNALING 1; INFLAMMATORY RESPONSES; TARGETING SUPPRESSOR; HUMAN KERATINOCYTES; SKIN; ACTIVATION; REGULATOR; MIR-155;
D O I
10.1111/jdv.13861
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Background MicroRNAs (miRNAs) gene expression regulators are altered in psoriasis suggesting their role in the pathogenesis. Objective To study expression changes of inflammation and toll-like receptor (TLR)-related miRNAs, miRNA-155, let-7i, miRNA-21, miRNA-146a and miRNA-223 in peripheral mononuclear cells (PBMCs) and miRNA-21, miRNA-146a and miRNA-223 in plasma, from chronic plaque-type psoriasis patients who were treatment-naive or had undergone a washout period (n = 11). MiRNAs were evaluated at baseline and after 11 (9-12) months [median (25th-75th percentile range)] of methotrexate (MTX) or topical (betamethasone plus calcipotriene) treatment. Methods MiRNA expression was analysed with quantitative real-time reverse transcription-polymerase chain reaction. Matched controls were studied. Results Psoriasis patients presented, at baseline, increased expression of miRNA-155, let-7i, miRNA-146a, miRNA-21 and miRNA-223 in PBMCs, plus miRNA-21, miRNA-146a and miRNA-223 in plasma. Receiver-operator characteristic (ROC) curve analysis and area under the curve (AUC) showed that expression of these miRNAs have the potential to distinguish between psoriasis and controls. At baseline, miRNA-155 expression in PBMCs correlated with Psoriasis Area Severity Index (PASI) [12 (8-14)] (Spearman r: 0.7140, P < 0.05) suggesting a role in psoriasis. After MTX or topical treatment, reduction in PASI was observed [87.5% (75-100)]; miRNA-155 expression in PBMCs decreased; plasma miRNA-21, miRNA-146a and miRNA-223 were down-regulated. ROC analysis showed that miRNA-155 expression in PBMCs from psoriasis patients have the potential to distinguish between patients' samples at baseline and after treatment (AUC: 0.942, sensitivity: 0.91; specificity: 0.91 values; maximum likelihood ratio = 10). After treatment, miRNA-146a expression in PBMCs increased; miRNA-155/miRNA-146a ratio decreased, suggestive of a regulatory feedback; let-7i expression decreased; miRNA-21 and miRNA-223 remained elevated. Conclusion In this exploratory study, psoriasis patients presented increased expression of miRNA-155 in PBMCs that correlated with PASI and decreased with disease remission. MiRNA-21, miRNA-146a and miRNA-223 in PBMCs and plasma were increased at baseline and differentially modulated, underscoring different roles of TLR-related miRNAs in psoriasis.
引用
收藏
页码:312 / 322
页数:11
相关论文
共 57 条
[1]   Atheroma plaque, metabolic syndrome and inflammation in patients with psoriasis [J].
Arias-Santiago, Salvador ;
Orgaz-Molina, Jacinto ;
Castellote-Caballero, Luisa ;
Angel Arrabal-Polo, Miguel ;
Garcia-Rodriguez, Sonia ;
Perandres-Lopez, Ruben ;
Carlos Ruiz, Jose ;
Naranjo-Sintes, Ramon ;
Zubiaur, Mercedes ;
Sancho, Jaime ;
Buendia-Eisman, Agustin .
EUROPEAN JOURNAL OF DERMATOLOGY, 2012, 22 (03) :337-344
[2]   Normal keratinocytes express Toll-like receptors (TLRs) 1, 2 and 5: modulation of TLR expression in chronic plaque psoriasis [J].
Baker, BS ;
Ovigne, JM ;
Powles, AV ;
Corcoran, S ;
Fry, L .
BRITISH JOURNAL OF DERMATOLOGY, 2003, 148 (04) :670-679
[3]   MicroRNAs: Target Recognition and Regulatory Functions [J].
Bartel, David P. .
CELL, 2009, 136 (02) :215-233
[4]  
Begon E, 2007, EUR J DERMATOL, V17, P497
[5]   Circulating miRNAs as potential biomarkers of therapy effectiveness in rheumatoid arthritis patients treated with anti-TNFα [J].
Castro-Villegas, Carmen ;
Perez-Sanchez, Carlos ;
Escudero, Alejandro ;
Filipescu, Ileana ;
Verdu, Miriam ;
Ruiz-Limon, Patricia ;
Angeles Aguirre, Ma ;
Jimenez-Gomez, Yolanda ;
Font, Pilar ;
Rodriguez-Ariza, Antonio ;
Ramon Peinado, Juan ;
Collantes-Estevez, Eduardo ;
Gonzalez-Conejero, Roco ;
Martinez, Constantino ;
Barbarroja, Nuria ;
Lopez-Pedrera, Chary .
ARTHRITIS RESEARCH & THERAPY, 2015, 17
[6]   A cellular Micro-RNA, let-7i, regulates toll-like receptor 4 expression and contributes to cholangiocyte immune responses against Cryptosporidium parvum infection [J].
Chen, Xian-Ming ;
Splinter, Patrick L. ;
O'Hara, Steven P. ;
LaRusso, Nicholas F. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (39) :28929-28938
[7]   1,25-Dihydroxyvitamin D Promotes Negative Feedback Regulation of TLR Signaling via Targeting MicroRNA-155-SOCS1 in Macrophages [J].
Chen, Yunzi ;
Liu, Weicheng ;
Sun, Tao ;
Huang, Yong ;
Wang, Youli ;
Deb, Dilip K. ;
Yoon, Dosuk ;
Kong, Juan ;
Thadhani, Ravi ;
Li, Yan Chun .
JOURNAL OF IMMUNOLOGY, 2013, 190 (07) :3687-3695
[8]   Impaired IFN-γ-dependent inflammatory responses in human keratinocytes overexpressing the suppressor of cytokine signaling 1 [J].
Federici, M ;
Giustizieri, ML ;
Scarponi, C ;
Girolomoni, G ;
Albanesi, C .
JOURNAL OF IMMUNOLOGY, 2002, 169 (01) :434-442
[9]   MicroRNA as type I interferon-regulated transcripts and modulators of the innate immune response [J].
Forster, Samuel C. ;
Tate, Michelle D. ;
Hertzog, Paul J. .
FRONTIERS IN IMMUNOLOGY, 2015, 6 :1-9
[10]   Abnormal Levels of Expression of Plasma MicroRNA-33 in Patients With Psoriasis [J].
Garcia-Rodriguez, S. ;
Arias-Santiago, S. ;
Orgaz-Molina, J. ;
Magro-Checa, C. ;
Valenzuela, I. ;
Navarro, P. ;
Naranjo-Sintes, R. ;
Sancho, J. ;
Zubiaur, M. .
ACTAS DERMO-SIFILIOGRAFICAS, 2014, 105 (05) :497-503