Go to the content. | Move to the navigation | Go to the site search | Go to the menu | Contacts | Accessibility

| Create Account

Beggio, Marianna (2017) Estrogen immunomodulation in systemic autoimmunity: evidences in in vitro models on a human myeloid cell line. [Ph.D. thesis]

Full text disponibile come:

[img]
Preview
PDF Document - Published Version
3320Kb

Abstract (english)

Background: Estrogens have an important role in determining immune system development, regulation and response to stimuli. Estrogens also influence pathogenesis and progression of autoimmune diseases, including Systemic Lupus Erythematosus (SLE), where there is a strong sex bias: female to male prevalence ratio is about 9:1. Estrogens, and in particular 17-β estradiol (E2), act as transcription factor through the binding to its specific receptors, ERα and ERβ. Among genes regulated by E2, Interferon α (IFNα) and B Lymphocyte Stimulator (BLyS) seem to be affected, and BLyS seems to be an IFN-inducible gene. Both cytokines are increased in SLE patients, indicating a link between hormones and cytokines induction in autoimmunity; BLyS over-expression can represent also a sign of the so called “IFN signature” characterizing systemic autoimmune diseases.
Objective: The aim of the present study was to evaluate the effects of E2 on BLyS mRNA and protein expression in a human myeloid cell line, in order to propose an in vitro model of estrogen systemic immunomodulation, also considering IFNα as a possible mediator of this signaling pathway.
Materials and Methods: U937 monocytes and U937-derived macrophages (treated with 50ng/mL Phorbol 12-Myristate 13-Acetate for 72 hours, Sigma-Aldrich) were exposed to E2 (Sigma-Aldrich) 100nM, 10nM, 1nM or 0.1nM. Cell viability was evaluated with Trypan Blue and Burker Chamber cell counting. Total RNA was extracted after 6, 24 and 48 hour administration, and culture medium was collected for protein quantification. Quantitative PCR was performed for BLyS and IFNα genes. GAPDH was used as reference gene. Primer concentration was 100nM and cDNA quantity was 25ng. Data were analyzed with 2-ΔΔCt method and statistical analysis was performed with REST-384© version 2 using Pair Wise Fixed Reallocation Randomisation Test©. ELISA assay, using a commercially available kit “Quantikine® ELISA” for Human BAFF/BLyS/TNFSF13B (R&D System) was performed for BLyS protein detection in culture supernatants. Data were normalized for total protein and differences in protein levels between treated and control cells during times were performed with multivariate analysis for repeated measures. The same protocols were used for treatment with exogenous human recombinant INFα (hr-IFNα, 1000IU/mL, Enzo Life Sciences), investigating BLyS mRNA expression at 6, 10, 24 and 48 hour and BLyS protein release at 6, 24 and 48 hour administration.
Results: E2 did not induce any modulation of BLyS gene expression at any time or concentration used, in both monocytes and derived-macrophages. BLyS protein release was increased during time, and the highest E2 doses induced BLyS protein mobilization in monocytes, while a BLyS release was noticed in derived-macrophages starting from 1nM E2. In monocytes, E2 induced a time-dependent IFNα up-regulation especially at doses 10nM and 1nM, while in differentiated macrophages E2 induced a significant IFNα down-regulation at 24 hours at doses 100nM and 10nM. IFNα treatment induced a significant up-regulation of BLyS, both in monocytes and in derived-macrophages at any time of treatment, but the effect was higher and faster in differentiated cells than in steady-state monocytes. Regarding BLyS protein release, IFNα treatment did not induce a significant BLyS increase compared with that observed in untreated cells.
Conclusion: Within 48-hour treatment E2 dose-dependently induces IFNα, but not BLyS expression, while exogenous IFNα affects BLyS transcription but not protein release. These findings suggest that estrogens could primarily have a role in the modulation of cytokines belonging to innate immunity, such as IFNα, with different effects depending on target cell phenotype and milieu. Estrogen modulation of adaptive immune response, here exemplified by BLyS, seems to be the result of estrogen-induced IFNα up-regulation, thus confirming the link between innate and adaptive immune activation in systemic autoimmunity.

Abstract (italian)

Background: Gli estrogeni svolgono un ruolo importante nel determinare lo sviluppo, la regolazione e la risposta agli stimoli del sistema immunitario. Essi sono implicati anche nella patogenesi e nella progressione delle malattie autoimmuni, come il Lupus Eritematoso Sistemico (LES), dove la prevalenza delle donne sugli uomini risulta essere di 9 a 1. Gli estrogeni, ed in particolare il 17-β estradiolo (E2), agiscono come fattori di trascrizione attraverso il legame con i loro specifici recettori, ERα ed ERβ. Tra i geni regolati da E2 troviamo l’Interferone α (IFNα) e B Lymphocyte Stimulator (BLyS); BLyS sembra essere un gene indotto anche da IFNα. Entrambe queste citochine si trovano ad alti livelli nei sieri dei pazienti con LES, indicando un possibile collegamento tra ormoni e induzione citochinica nell’autoimmunità; l’over-espressione di BLyS può anche rappresentare un segnale della cosiddetta “IFN signature”, che caratterizza le malattie autoimmuni sistemiche.
Obiettivo: Lo scopo del presente studio è stato quello di valutare gli effetti di E2 sull’espressione di BLyS mRNA e proteina in una linea cellulare mieloide umana, così da proporre un modello in vitro di immunomodulazione sistemica indotta da estrogeni, considerando IFNα come un possibile mediatore di questa via di segnale.
Materiali e Metodi: Cellule umane U937, monocitarie e simil-macrofagiche (trattati con 50ng/mL di Forbolo 12-Miristato 13-Acetato, Sigma-Aldrich), sono state trattate con E2 (Sigma-Aldrich) alle concentrazioni 100nM, 10nM, 1nM, 0.1nM. La vitalità cellulare è stata valutata mediante conta cellulare con il colorante vitale Trypan Blue e Camera di Burker. L’RNA totale è stato estratto dopo 6, 24 e 48 ore dal trattamento, e il medium di coltura è stato raccolto per la quantificazione proteica. La PCR quantitativa (qPCR) è stata eseguita per i geni BLyS e IFNα. GAPDH è stato utilizzato come gene reference. Sono stati utilizzati i primer alla concentrazione 100nM e cDNA nella quantità di 25ng. I dati sono stati analizzati con il metodo 2-ΔΔCt e l’analisi statistica è stata eseguita con REST-384© version 2 using Pair Wise Fixed Reallocation Randomisation Test©. Per determinare la quantità di proteine nel surnatante di coltura è stato utilizzato il kit ELISA commerciale “Quantikine® ELISA” for Human BAFF/BLyS/TNFSF13B (R&D System). I livelli di BLyS proteina sono stati normalizzati per i livelli di proteine totali e le differenze nei livelli di proteina tra cellule trattate e di controllo sono stati valutati con un’analisi multivariata per misure ripetute. Gli stessi protocolli sono stati utilizzati per il trattamento con IFNα ricombinante umano esogeno (hr-IFNα, 1000IU/mL, Enzo Life Sciences), indagando l’espressione dell’mRNA di BLyS a 6, 10, 24 e 48 ore e il rilascio di BLyS proteina a 6, 24 e 48 ore dal trattamento.
Risultati: E2 non induce modulazione dell’espressione genica di BLyS ai tempi e alle concentrazioni testate, sia nei monociti che nei macrofagi-derivati. I livelli di BLyS proteina nel surnatante di coltura aumentano nel tempo, le più alte dosi di E2 inducono la mobilizzazione e il rilascio di BLyS in coltura nei monociti, mentre nei macrofagi-derivati si è notato un rilascio di BLyS partendo dalla concentrazione di E2 1nM. Nei monociti E2 induce un’up-regolazione tempo-dipendente di IFNα, specialmente alle dosi 10nM e 1nM, mentre nei macrofagi differenziati E2 induce una significativa down-regolazione di IFNα a 24 ore, alle dosi 100nM e 10nM. Il trattamento con IFNα induce una significativa up-regolazione di BLyS, sia nei monociti che nei macrofagi-derivati ad ogni tempo di trattamento, ma gli effetti sono risultati più rapidi e più marcati nei macrofagi rispetto ai monociti. Per quanto riguarda il rilascio di BLyS proteina, il trattamento con IFNα non ha indotto un significativo aumento di BLyS rispetto alle cellule non trattate.
Conclusioni: Entro 48 ore, il trattamento con E2 modifica in maniera dose-dipendente l’espressione di IFNα, ma non quella di BLyS, mentre IFNα esogeno influisce sulla trascrizione di BLyS, ma non sul rilascio della proteina stessa. Queste evidenze suggeriscono che gli estrogeni possono avere primariamente un ruolo nella modulazione di citochine appartenenti all’immunità innata, come l’IFNα, con effetti differenti dipendenti dal fenotipo cellulare e dal milieu citochinico. La modulazione estrogenica della risposta immunitaria adattativa, qui esemplificata da BLyS, sembra essere il risultato dell’up-regolazione di IFNα indotta da estrogeni, a conferma della stretta inter-relazione tra immunità innata e adattativa nell’autoimmunità sistemica.

Statistiche Download - Aggiungi a RefWorks
EPrint type:Ph.D. thesis
Tutor:Doria, Andrea
Ph.D. course:Ciclo 29 > Corsi 29 > SCIENZE MEDICHE, CLINICHE E SPERIMENTALI
Data di deposito della tesi:18 January 2017
Anno di Pubblicazione:31 January 2017
Key Words:Systemic autoimmunity, Estrogens, BLyS, IFNα, Human myeloid cell line
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/16 Reumatologia
Struttura di riferimento:Dipartimenti > Dipartimento di Scienze Cardiologiche, Toraciche e Vascolari
Codice ID:9836
Depositato il:09 Nov 2017 12:13
Simple Metadata
Full Metadata
EndNote Format

Bibliografia

I riferimenti della bibliografia possono essere cercati con Cerca la citazione di AIRE, copiando il titolo dell'articolo (o del libro) e la rivista (se presente) nei campi appositi di "Cerca la Citazione di AIRE".
Le url contenute in alcuni riferimenti sono raggiungibili cliccando sul link alla fine della citazione (Vai!) e tramite Google (Ricerca con Google). Il risultato dipende dalla formattazione della citazione.

[1] Ruggieri A, Anticoli S, D'Ambrosio A, Giordani L, Viora M. The influence of sex and gender on immunity, infection and vaccination. Ann Ist Super Sanita. 2016;52:198-204 Cerca con Google

[2] Zandman-Goddard G, Peeva E, Shoenfeld Y. Gender and autoimmunity. Autoimmun Rev. 2007;6:366-72 Cerca con Google

[3] Heldring N, Pike A, Andersson S, Matthews J, Cheng G, Hartman J, Tujague M, Ström A, Treuter E, Warner M, Gustafsson JA. Estrogen receptors: how do they signal and what are their targets. Physiol Rev. 2007;87:905-31 Cerca con Google

[4] Tanriverdi F, Silveira LF, MacColl GS, Bouloux PM. The hypothalamic-pituitary-gonadal axis: immune function and autoimmunity. J Endocrinol. 2003;176:293-304 Cerca con Google

[5] Doria A, Ghirardello A, Iaccarino L, Zampieri S, Punzi L, Tarricone E, Ruffatti A, Sulli A, Sarzi-Puttini PC, Gambari PF, Cutolo M. Pregnancy, cytokines, and disease activity in systemic lupus erythematosus. Arthritis Rheum. 2004;51:989-95 Cerca con Google

[6] Costenbader KH, Feskanich D, Stampfer MJ, Karlson EW. Reproductive and menopausal factors and risk of systemic lupus erythematosus in women. Arthritis Rheum. 2007;56:1251-62 Cerca con Google

[7] Bernier MO, Mikaeloff Y, Hudson M, Suissa S. Combined oral contraceptive use and the risk of systemic lupus erythematosus. Arthritis Rheum. 2009;61:476-81 Cerca con Google

[8] Cutolo M, Sulli A, Straub RH. Estrogen metabolism and autoimmunity. Autoimmun Rev. 2012;11:A460-4 Cerca con Google

[9] Festing MFW. Inbred strains of mice. Mouse genome. 1997;95:519-86 Cerca con Google

[10] Roubinian JR, Talal N, Greenspan JS, Goodman JR, Siiteri PK. Effect of castration and sex hormone treatment on survival, anti-nucleic acid antibodies, and glomerulonephritis in NZB/NZW F1 mice. J Exp Med. 1978;147:1568-83 Cerca con Google

[11] Bynoté KK, Hackenberg JM, Korach KS, Lubahn DB, Lane PH, Gould KA. Estrogen receptor-alpha deficiency attenuates autoimmune disease in (NZB x NZW)F1 mice. Genes Immun. 2008;9:137-52 Cerca con Google

[12] Bassi N, Luisetto R, Ghirardello A, Gatto M, Valente M, Della Barbera M, Nalotto L, Punzi L, Doria A. 17-β-estradiol affects BLyS serum levels and the nephritogenic autoantibody network accelerating glomerulonephritis in NZB/WF1 mice. Lupus. 2015;24:382-91 Cerca con Google

[13] Li J, McMurray RW. Effects of estrogen receptor subtype-selective agonists on autoimmune disease in lupus-prone NZB/NZW F1 mouse model. Clin Immunol. 2007;123:219-26 Cerca con Google

[14] Cutolo M, Capellino S, Montagna P, Ghiorzo P, Sulli A, Villaggio B. Sex hormone modulation of cell growth and apoptosis of the human monocytic/macrophage cell line. Arthritis Res Ther. 2005;7:R1124-32 Cerca con Google

[15] Thongngarm T, Jenkins JK, Ndebele K, McMurray RW. Estrogen and progesterone modulate monocyte cell cycle progression and apoptosis. Am J Reprod Immunol. 2003;49:129-38 Cerca con Google

[16] Grimaldi CM, Cleary J, Dagtas AS, Moussai D, Diamond B. Estrogen alters thresholds for B cell apoptosis and activation. J Clin Invest. 2002;109:1625-33 Cerca con Google

[17] Bynoe MS, Grimaldi CM, Diamond B. Estrogen up-regulates Bcl-2 and blocks tolerance induction of naive B cells. Proc Natl Acad Sci U S A. 2000;97:2703-8 Cerca con Google

[18] Panchanathan R, Choubey D. Murine BAFF expression is up-regulated by estrogen and interferons: implications for sex bias in the development of autoimmunity. Mol Immunol. 2013;53:15-23 Cerca con Google

[19] Devey ME, Lee SR, Le Page S, Feldman R, Isenberg DA. Serial studies of the IgG subclass and functional affinity of DNA antibodies in systemic lupus erythematosus. J Autoimmun. 1988;1:483-94 Cerca con Google

[20] Pauklin S, Sernández IV, Bachmann G, Ramiro AR, Petersen-Mahrt SK. Estrogen directly activates AID transcription and function. J Exp Med. 2009;206:99-111 Cerca con Google

[21] Jones BG, Penkert RR, Xu B, Fan Y, Neale G, Gearhart PJ, Hurwitz JL. Binding of estrogen receptors to switch sites and regulatory elements in the immunoglobulin heavy chain locus of activated B cells suggests a direct influence of estrogen on antibody expression. Mol Immunol. 2016;77:97-102 Cerca con Google

[22] Walker SE Estrogen and autoimmune disease. Clin Rev Allergy Immunol. 2011;40:60-5 Cerca con Google

[23] Rastin M, Hatef MR, Tabasi N, Sheikh A, Morad Abbasi J, Mahmoudi M. Sex hormones and peripheral white blood cell subsets in systemic lupus erythematosus patients. Iran J Immunol. 2007;4:110-5 Cerca con Google

[24] Ding C, Yan J. Regulation of autoreactive B cells: checkpoints and activation. Arch Immunol Ther Exp (Warsz). 2007;55:83-9 Cerca con Google

[25] Lleo A, Invernizzi P, Gao B, Podda M, Gershwin ME. Definition of human autoimmunity--autoantibodies versus autoimmune disease. Autoimmun Rev. 2010;9:A259-66 Cerca con Google

[26] Liao W, Lin JX, Leonard WJ. Interleukin-2 at the crossroads of effector responses, tolerance, and immunotherapy. Immunity. 2013;38:13-25 Cerca con Google

[27] Maret A, Coudert JD, Garidou L, Foucras G, Gourdy P, Krust A, Dupont S, Chambon P, Druet P, Bayard F, Guéry JC. Estradiol enhances primary antigen-specific CD4 T cell responses and Th1 development in vivo. Essential role of estrogen receptor alpha expression in hematopoietic cells. Eur J Immunol. 2003;33:512-21 Cerca con Google

[28] Zen M, Ghirardello A, Iaccarino L, Tonon M, Campana C, Arienti S, Rampudda M, Canova M, Doria A. Hormones, immune response, and pregnancy in healthy women and SLE patients. Swiss Med Wkly. 2010;140:187-201 Cerca con Google

[29] Sakaguchi S, Sakaguchi N. Regulatory T cells in immunologic self-tolerance and autoimmune disease. Int Rev Immunol. 2005;24:211-26 Cerca con Google

[30] Erlebacher A. Mechanisms of T cell tolerance towards the allogeneic fetus. Nat Rev Immunol. 2013;13:23-33 Cerca con Google

[31] Hughes GC, Choubey D. Modulation of autoimmune rheumatic diseases by oestrogen and progesterone. Nat Rev Rheumatol. 2014;10:740-51 Cerca con Google

[32] Hagberg N, Rönnblom L. Systemic Lupus Erythematosus-A Disease with A Dysregulated Type I Interferon System. Scand J Immunol. 2015;82:199-207 Cerca con Google

[33] Gürtler C, Bowie AG. Innate immune detection of microbial nucleic acids. Trends Microbiol. 2013;21:413-20 Cerca con Google

[34] Uzé G, Schreiber G, Piehler J, Pellegrini S. The receptor of the type I interferon family. Curr Top Microbiol Immunol. 2007;316:71-95 Cerca con Google

[35] Paul F, Pellegrini S, Uzé G. IFNA2: The prototypic human alpha interferon. Gene. 2015;567:132-7 Cerca con Google

[36] Hagberg; Rönnblom L. The importance of the type I interferon system in autoimmunity. Clin Exp Rheumatol. 2016;34:21-4 Cerca con Google

[37] Burman P, Karlsson FA, Oberg K, Alm G. Autoimmune thyroid disease in interferon-treated patients. Lancet. 1985;2:100-1 Cerca con Google

[38] Black CM, Silman AJ, Herrick AI, Denton CP, Wilson H, Newman J, Pompon L, Shi-Wen X. Interferon-alpha does not improve outcome at one year in patients with diffuse cutaneous scleroderma: results of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 1999;42:299-305 Cerca con Google

[39] Lövgren T, Eloranta ML, Båve U, Alm GV, Rönnblom L. Induction of interferon-alpha production in plasmacytoid dendritic cells by immune complexes containing nucleic acid released by necrotic or late apoptotic cells and lupus IgG. Arthritis Rheum. 2004;50:1861-72 Cerca con Google

[40] Munoz LE, van Bavel C, Franz S, Berden J, Herrmann M, van der Vlag J. Apoptosis in the pathogenesis of systemic lupus erythematosus. Lupus. 2008;17:371-5 Cerca con Google

[41] Vallin H, Blomberg S, Alm GV, Cederblad B, Rönnblom L. Patients with systemic lupus erythematosus (SLE) have a circulating inducer of interferon-alpha (IFN-alpha) production acting on leucocytes resembling immature dendritic cells. Clin Exp Immunol. 1999;115:196-202 Cerca con Google

[42] Vallin H, Perers A, Alm GV, Rönnblom L. Anti-double-stranded DNA antibodies and immunostimulatory plasmid DNA in combination mimic the endogenous IFN-alpha inducer in systemic lupus erythematosus. J Immunol. 1999;163:6306-13 Cerca con Google

[43] 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;197:711-23 Cerca con Google

[44] Mathian A, Weinberg A, Gallegos M, Banchereau J, Koutouzov S. IFN-alpha induces early lethal lupus in preautoimmune (New Zealand Black x New Zealand White) F1 but not in BALB/c mice. J Immunol. 2005;174:2499-506 Cerca con Google

[45] Barrat FJ, Meeker T, Chan JH, Guiducci C, Coffman RL. Treatment of lupus-prone mice with a dual inhibitor of TLR7 and TLR9 leads to reduction of autoantibody production and amelioration of disease symptoms. Eur J Immunol. 2007;37:3582-6 Cerca con Google

[46] Kawasaki T, Kawai T, Akira S. Recognition of nucleic acids by pattern-recognition receptors and its relevance in autoimmunity. Immunol Rev. 2011;243:61-73 Cerca con Google

[47] Rifkin IR, Leadbetter EA, Busconi L, Viglianti G, Marshak-Rothstein A. Toll-like receptors, endogenous ligands, and systemic autoimmune disease. Immunol Rev. 2005;204:27-42 Cerca con Google

[48] Leadbetter EA, Rifkin IR, Hohlbaum AM, Beaudette BC, Shlomchik MJ, Marshak-Rothstein A. Chromatin-IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors. Nature. 2002;416:603-7 Cerca con Google

[49] Gregersen PK, Behrens TW. Genetics of autoimmune diseases--disorders of immune homeostasis. Nat Rev Genet. 2006;7:917-28 Cerca con Google

[50] Klein SL, Jedlicka A, Pekosz A. The Xs and Y of immune responses to viral vaccines. Lancet Infect Dis. 2010;10:338-49 Cerca con Google

[51] Meier A, Chang JJ, Chan ES, Pollard RB, Sidhu HK, Kulkarni S, Wen TF, Lindsay RJ, Orellana L, Mildvan D, Bazner S, Streeck H, Alter G, Lifson JD, Carrington M, Bosch RJ, Robbins GK, Altfeld M. Sex differences in the Toll-like receptor-mediated response of plasmacytoid dendritic cells to HIV-1. Nat Med. 2009;15:955-9 Cerca con Google

[52] Seillet C, Laffont S, Trémollières F, Rouquié N, Ribot C, Arnal JF, Douin-Echinard V, Gourdy P, Guéry JC. The TLR-mediated response of plasmacytoid dendritic cells is positively regulated by estradiol in vivo through cell-intrinsic estrogen receptor α signaling. Blood. 2012;119:454-64 Cerca con Google

[53] Panchanathan R, Liu H, Leung YK, Ho SM, Choubey D. Bisphenol A (BPA) stimulates the interferon signaling and activates the inflammasome activity in myeloid cells. Mol Cell Endocrinol. 2015;415:45-55 Cerca con Google

[54] Dong G, Fan H, Yang Y, Zhao G, You M, Wang T, Hou Y. 17β-Estradiol enhances the activation of IFN-α signaling in B cells by down-regulating the expression of let-7e-5p, miR-98-5p and miR-145a-5p that target IKKε. Biochim Biophys Acta. 2015;1852:1585-98 Cerca con Google

[55] Schneider P, MacKay F, Steiner V, Hofmann K, Bodmer JL, Holler N, Ambrose C, Lawton P, Bixler S, Acha-Orbea H, Valmori D, Romero P, Werner-Favre C, Zubler RH, Browning JL, Tschopp J. BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth. J Exp Med. 1999;189:1747-56 Cerca con Google

[56] Batten M, Groom J, Cachero TG, Qian F, Schneider P, Tschopp J, Browning JL, Mackay F. BAFF mediates survival of peripheral immature B lymphocytes. J Exp Med. 2000;192:1453-66 Cerca con Google

[57] Moore PA, Belvedere O, Orr A, Pieri K, LaFleur DW, Feng P, Soppet D, Charters M, Gentz R, Parmelee D, Li Y, Galperina O, Giri J, Roschke V, Nardelli B, Carrell J, Sosnovtseva S, Greenfield W, Ruben SM, Olsen HS, Fikes J, Hilbert DM. BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator. Science. 1999;285:260-3 Cerca con Google

[58] Scapini P, Nardelli B, Nadali G, Calzetti F, Pizzolo G, Montecucco C, Cassatella MA. G-CSF-stimulated neutrophils are a prominent source of functional BLyS. J Exp Med. 2003;197:297-302 Cerca con Google

[59] Scapini P, Carletto A, Nardelli B, Calzetti F, Roschke V, Merigo F, Tamassia N, Pieropan S, Biasi D, Sbarbati A, Sozzani S, Bambara L, Cassatella MA. Proinflammatory mediators elicit secretion of the intracellular B-lymphocyte stimulator pool (BLyS) that is stored in activated neutrophils: implications for inflammatory diseases. Blood. 2005;105:830-7 Cerca con Google

[60] Thompson JS, Bixler SA, Qian F, Vora K, Scott ML, Cachero TG, Hession C, Schneider P, Sizing ID, Mullen C, Strauch K, Zafari M, Benjamin CD, Tschopp J, Browning JL, Ambrose C. BAFF-R, a newly identified TNF receptor that specifically interacts with BAFF. Science. 2001;293:2108-11 Cerca con Google

[61] Vincent FB, Morand EF, Schneider P, Mackay F. The BAFF/APRIL system in SLE pathogenesis. Nat Rev Rheumatol. 2014;10:365-73 Cerca con Google

[62] Bossen C, Tardivel A, Willen L, Fletcher CA, Perroud M, Beermann F, Rolink AG, Scott ML, Mackay F, Schneider P. Mutation of the BAFF furin cleavage site impairs B-cell homeostasis and antibody responses. Eur J Immunol. 2011;41:787-97 Cerca con Google

[63] Sutherland AP, Ng LG, Fletcher CA, Shum B, Newton RA, Grey ST, Rolph MS, Mackay F, Mackay CR. BAFF augments certain Th1-associated inflammatory responses. J Immunol. 2005;174:5537-44 Cerca con Google

[64] Thien M, Phan TG, Gardam S, Amesbury M, Basten A, Mackay F, Brink R. Excess BAFF rescues self-reactive B cells from peripheral deletion and allows them to enter forbidden follicular and marginal zone niches. Immunity. 2004;20:785-98 Cerca con Google

[65] Huard B, Schneider P, Mauri D, Tschopp J, French LE. T cell costimulation by the TNF ligand BAFF. J Immunol. 2001;167:6225-3 Cerca con Google

[66] Huard B, Arlettaz L, Ambrose C, Kindler V, Mauri D, Roosnek E, Tschopp J, Schneider P, French LE. BAFF production by antigen-presenting cells provides T cell co-stimulation. Int Immunol. 2004;16:467-75 Cerca con Google

[67] Mackay F, Woodcock SA, Lawton P, Ambrose C, Baetscher M, Schneider P, Tschopp J, Browning JL. Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations. J Exp Med. 1999;190:1697-710 Cerca con Google

[68] Fletcher CA, Groom JR, Woehl B, Leung H, Mackay C, Mackay F. Development of autoimmune nephritis in genetically asplenic and splenectomized BAFF transgenic mice. J Autoimmun. 2011;36:125-34 Cerca con Google

[69] Gross JA, Johnston J, Mudri S, Enselman R, Dillon SR, Madden K, Xu W, Parrish-Novak J, Foster D, Lofton-Day C, Moore M, Littau A, Grossman A, Haugen H, Foley K, Blumberg H, Harrison K, Kindsvogel W, Clegg CH. TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease. Nature. 2000;404:995-9 Cerca con Google

[70] Gross JA, Dillon SR, Mudri S, Johnston J, Littau A, Roque R, Rixon M, Schou O, Foley KP, Haugen H, McMillen S, Waggie K, Schreckhise RW, Shoemaker K, Vu T, Moore M, Grossman A, Clegg CH. TACI-Ig neutralizes molecules critical for B cell development and autoimmune disease. impaired B cell maturation in mice lacking BLyS. Immunity. 2001;15:289-302 Cerca con Google

[71] Petri M, Stohl W, Chatham W, McCune WJ, Chevrier M, Ryel J, Recta V, Zhong J, Freimuth W. Association of plasma B lymphocyte stimulator levels and disease activity in systemic lupus erythematosus. Arthritis Rheum. 2008;58:2453-9 Cerca con Google

[72] Vincent FB, Saulep-Easton D, Figgett WA, Fairfax KA, Mackay F. The BAFF/APRIL system: emerging functions beyond B cell biology and autoimmunity. Cytokine Growth Factor Rev. 2013;24:203-15 Cerca con Google

[73] Baker KP, Edwards BM, Main SH, Choi GH, Wager RE, Halpern WG, Lappin PB, Riccobene T, Abramian D, Sekut L, Sturm B, Poortman C, Minter RR, Dobson CL, Williams E, Carmen S, Smith R, Roschke V, Hilbert DM, Vaughan TJ, Albert VR. Generation and characterization of LymphoStat-B, a human monoclonal antibody that antagonizes the bioactivities of B lymphocyte stimulator. Arthritis Rheum. 2003;48:3253-65 Cerca con Google

[74] López P, Scheel-Toellner D, Rodríguez-Carrio J, Caminal-Montero L, Gordon C, Suárez A. Interferon-α-induced B-lymphocyte stimulator expression and mobilization in healthy and systemic lupus erythematosus monocytes. Rheumatology (Oxford). 2014;53:2249-58 Cerca con Google

[75] 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;25:402-8 Cerca con Google

[76] Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248-54 Cerca con Google

[77] Pfaffl MW, Horgan GW, Dempfle L. Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res. 2002;30:e36 Cerca con Google

[78] Doria A, Cutolo M, Ghirardello A, Zen M, Villalta D, Tincani A, Punzi L, Iaccarino L, Petri M. Effect of pregnancy on serum cytokines in SLE patients. Arthritis Res Ther. 2012;14:R66 Cerca con Google

[79] Drehmer MN, Suterio DG, Muniz YC, de Souza IR, Löfgren SE. BAFF Expression is Modulated by Female Hormones in Human Immune Cells. Biochem Genet. 2016;54:722-30 Cerca con Google

[80] Campesi I, Marino M, Montella A, Pais S, Franconi F. Sex Differences in Estrogen Receptor α and β Levels and Activation Status in LPS-Stimulated Human Macrophages. J Cell Physiol. 2017;232:340-45 Cerca con Google

[81] Mor G, Sapi E, Abrahams VM, Rutherford T, Song J, Hao XY, Muzaffar S, Kohen F. Interaction of the estrogen receptors with the Fas ligand promoter in human monocytes. J Immunol. 2003;170:114-22 Cerca con Google

[82] Calippe B, Douin-Echinard V, Laffargue M, Laurell H, Rana-Poussine V, Pipy B, Guéry JC, Bayard F, Arnal JF, Gourdy P. Chronic estradiol administration in vivo promotes the proinflammatory response of macrophages to TLR4 activation: involvement of the phosphatidylinositol 3-kinase pathway. J Immunol. 2008;180:7980-8 Cerca con Google

[83] Ghirardello A, Gizzo S, Noventa M, Quaranta M, Vitagliano A, Gallo N, Pantano G, Beggio M, Cosma C, Gangemi M, Plebani M, Doria A. Acute immunomodulatory changes during controlled ovarian stimulation: evidence from the first trial investigating the short-term effects of estradiol on biomarkers and B cells involved in autoimmunity. J Assist Reprod Genet. 2015;32:1765-72 Cerca con Google

[84] Tasker C, Ding J, Schmolke M, Rivera-Medina A, García-Sastre A, Chang TL. 17β-estradiol protects primary macrophages against HIV infection through induction of interferon-alpha. Viral Immunol. 2014;27:140-50 Cerca con Google

[85] Yao Y, Richman L, Higgs BW, Morehouse CA, de los Reyes M, Brohawn P, Zhang J, White B, Coyle AJ, Kiener PA, Jallal B. Neutralization of interferon-alpha/beta-inducible genes and downstream effect in a phase I trial of an anti-interferon-alpha monoclonal antibody in systemic lupus erythematosus. Arthritis Rheum. 2009;60:1785-96 Cerca con Google

[86] Morimoto AM, Flesher DT, Yang J, Wolslegel K, Wang X, Brady A, Abbas AR, Quarmby V, Wakshull E, Richardson B, Townsend MJ, Behrens TW. Association of endogenous anti-interferon-α autoantibodies with decreased interferon-pathway and disease activity in patients with systemic lupus erythematosus. Arthritis Rheum. 2011;63:2407-15 Cerca con Google

[87] Gomez AM, Ouellet M, Tremblay MJ. HIV-1-triggered release of type I IFN by plasmacytoid dendritic cells induces BAFF production in monocytes. J Immunol. 2015;194:2300-8 Cerca con Google

Download statistics

Solo per lo Staff dell Archivio: Modifica questo record