{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:14:31Z","timestamp":1790640871068,"version":"4.1.0"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,10,30]],"date-time":"2020-10-30T00:00:00Z","timestamp":1604016000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,10,30]],"date-time":"2020-10-30T00:00:00Z","timestamp":1604016000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["FIS 16\/00032"],"award-info":[{"award-number":["FIS 16\/00032"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["FIS 16\/00032"],"award-info":[{"award-number":["FIS 16\/00032"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["RETICS RD16\/0012 RIER"],"award-info":[{"award-number":["RETICS RD16\/0012 RIER"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Mol and Cell Biol"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The clinical efficacy of specific interleukin-6 inhibitors has confirmed the central role of IL6 in rheumatoid arthritis (RA). However the local role of IL6, in particular in synovial fibroblasts (SF) as a direct cellular target to IL6\/sIL6R signal is not well characterized. The purpose of the study was to characterize the crosstalk between TNF\u03b1 and IL6\/sIL6R signaling to the effector pro-inflammatory response of SF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      SF lines were stimulated with either TNF\u03b1, IL6\/sIL6R, or both together, for the time and dose indicated for each experiment, and where indicated, cells were treated with inhibitors actinomycin D, adalimumab, ruxolitinib and cycloheximide. mRNA expression of cytokines, chemokines and matrix metalloproteases (MMPs) were analyzed by quantitative RT-PCR. Level of IL8\/CXCL8 and CCL8 in culture supernatants was measured by ELISA. Mononuclear and polymorphonuclear cells migration assays were assessed by transwell using conditioned medium from SF cultures. Statistical analyses were performed as indicated in the corresponding figure legends and a\n                      <jats:italic>p<\/jats:italic>\n                      -value &lt;\u20090.05 was considered statistically significant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The stimulation of SF with IL6\/sIL6R and TNF\u03b1, cooperatively promotes the expression of mono- and lymphocytic chemokines such as IL6, CCL8 and CCL2, as well as matrix degrading enzymes such as MMP1, while inhibiting the induction of central neutrophil chemokines such as IL8\/CXCL8. These changes in the pattern of chemokines expression resulted in reduced polymorphonuclear (PMN) and increased mononuclear cells (MNC) chemoattraction by SF. Mechanistic analyses of the temporal expression of genes demonstrated that the cooperative regulation mediated by these two factors is mostly induced through de novo transcriptional mechanisms activated by IL6\/sIL6R. Furthermore, we also demonstrate that TNF\u03b1 and IL6\/sIL6R cooperation is partially mediated by the expression of secondary factors signaling through JAK\/STAT pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results point out to a highly orchestrated response to IL6 in TNF\u03b1-induced SF and provide additional insights into the role of IL6\/sIL6R in the context of RA, highlighting the contribution of IL6\/sIL6R to the interplay of SF with other inflammatory cells.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12860-020-00317-7","type":"journal-article","created":{"date-parts":[[2020,10,30]],"date-time":"2020-10-30T06:03:01Z","timestamp":1604037781000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["IL6\/sIL6R regulates TNF\u03b1-inflammatory response in synovial fibroblasts through modulation of transcriptional and post-transcriptional mechanisms"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5296-7374","authenticated-orcid":false,"given":"Alvaro","family":"Valin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel J.","family":"Del Rey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Municio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Usategui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Romero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Fern\u00e1ndez-Felipe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan D.","family":"Ca\u00f1ete","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco J.","family":"Blanco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolanda","family":"Ruano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Criado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 L.","family":"Pablos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,10,30]]},"reference":[{"key":"317_CR1","doi-asserted-by":"publisher","first-page":"S4","DOI":"10.1186\/ar1918","volume":"8 Suppl 2","author":"PE Lipsky","year":"2006","unstructured":"Lipsky PE. Interleukin-6 and rheumatic diseases. Arthritis Res Ther. 2006;8 Suppl 2:S4.","journal-title":"Arthritis Res Ther"},{"issue":"6","key":"317_CR2","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1002\/art.1780310614","volume":"31","author":"FA Houssiau","year":"1988","unstructured":"Houssiau FA, Devogelaer JP, Van Damme J, de Deuxchaisnes CN, Van Snick J. Interleukin-6 in synovial fluid and serum of patients with rheumatoid arthritis and other inflammatory arthritides. Arthritis Rheum. 1988;31(6):784\u20138.","journal-title":"Arthritis Rheum"},{"issue":"5","key":"317_CR3","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1080\/09629359890875","volume":"7","author":"T Robak","year":"1998","unstructured":"Robak T, Gladalska A, Stepien H, Robak E. Serum levels of interleukin-6 type cytokines and soluble interleukin-6 receptor in patients with rheumatoid arthritis. Mediat Inflamm. 1998;7(5):347\u201353.","journal-title":"Mediat Inflamm"},{"key":"317_CR4","first-page":"135","volume":"254","author":"T Kishimoto","year":"1989","unstructured":"Kishimoto T, Taga T, Yamasaki K, Matsuda T, Tang B, Muraguchi A, Horii Y, Suematsu S, Hirata Y, Yawata H, et al. Normal and abnormal regulation of human B cell differentiation by a new cytokine, BSF2\/IL-6. Adv Exp Med Biol. 1989;254:135\u201343.","journal-title":"Adv Exp Med Biol"},{"issue":"9","key":"317_CR5","doi-asserted-by":"crossref","first-page":"3347","DOI":"10.4049\/jimmunol.144.9.3347","volume":"144","author":"GS Firestein","year":"1990","unstructured":"Firestein GS, Alvaro-Gracia JM, Maki R. Quantitative analysis of cytokine gene expression in rheumatoid arthritis. J Immunol. 1990;144(9):3347\u201353.","journal-title":"J Immunol"},{"issue":"6","key":"317_CR6","doi-asserted-by":"publisher","first-page":"3202","DOI":"10.4049\/jimmunol.171.6.3202","volume":"171","author":"MA Nowell","year":"2003","unstructured":"Nowell MA, Richards PJ, Horiuchi S, Yamamoto N, Rose-John S, Topley N, Williams AS, Jones SA. Soluble IL-6 receptor governs IL-6 activity in experimental arthritis: blockade of arthritis severity by soluble glycoprotein 130. J Immunol. 2003;171(6):3202\u20139.","journal-title":"J Immunol"},{"issue":"8","key":"317_CR7","first-page":"1510","volume":"24","author":"A Desgeorges","year":"1997","unstructured":"Desgeorges A, Gabay C, Silacci P, Novick D, Roux-Lombard P, Grau G, Dayer JM, Vischer T, Guerne PA. Concentrations and origins of soluble interleukin 6 receptor-alpha in serum and synovial fluid. J Rheumatol. 1997;24(8):1510\u20136.","journal-title":"J Rheumatol"},{"issue":"5","key":"317_CR8","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1038\/ni.3153","volume":"16","author":"CA Hunter","year":"2015","unstructured":"Hunter CA, Jones SA. IL-6 as a keystone cytokine in health and disease. Nat Immunol. 2015;16(5):448\u201357.","journal-title":"Nat Immunol"},{"issue":"1","key":"317_CR9","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1002\/jbmr.5650110113","volume":"11","author":"S Kotake","year":"1996","unstructured":"Kotake S, Sato K, Kim KJ, Takahashi N, Udagawa N, Nakamura I, Yamaguchi A, Kishimoto T, Suda T, Kashiwazaki S. Interleukin-6 and soluble interleukin-6 receptors in the synovial fluids from rheumatoid arthritis patients are responsible for osteoclast-like cell formation. J Bone Miner Res. 1996;11(1):88\u201395.","journal-title":"J Bone Miner Res"},{"issue":"3","key":"317_CR10","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1189\/jlb.0911458","volume":"91","author":"HM McGettrick","year":"2012","unstructured":"McGettrick HM, Butler LM, Buckley CD, Rainger GE, Nash GB. Tissue stroma as a regulator of leukocyte recruitment in inflammation. J Leukoc Biol. 2012;91(3):385\u2013400.","journal-title":"J Leukoc Biol"},{"key":"317_CR11","first-page":"1","volume":"0","author":"K Kaneshiro","year":"2019","unstructured":"Kaneshiro K, Sakai Y, Suzuki K, Uchida K, Tateishi K, Terashima Y, Kawasaki Y, Shibanuma N, Yoshida K, Hashiramoto A. Interleukin-6 and tumour necrosis factor-\u03b1 cooperatively promote cellcycle regulators and proliferate rheumatoid arthritis fibroblast-like synovial cells. Scand J Rheumatol. 2019;0:1\u20139.","journal-title":"Scand J Rheumatol"},{"issue":"1","key":"317_CR12","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1038\/nchembio.2211","volume":"13","author":"DS Jones","year":"2017","unstructured":"Jones DS, Jenney AP, Swantek JL, Burke JM, Lauffenburger DA, Sorger PK. Profiling drugs for rheumatoid arthritis that inhibit synovial fibroblast activation. Nat Chem Biol. 2017;13(1):38\u201345.","journal-title":"Nat Chem Biol"},{"issue":"1","key":"317_CR13","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/nrrheum.2015.169","volume":"12","author":"GD Kalliolias","year":"2016","unstructured":"Kalliolias GD, Ivashkiv LB. TNF biology, pathogenic mechanisms and emerging therapeutic strategies. Nat Rev Rheumatol. 2016;12(1):49\u201362.","journal-title":"Nat Rev Rheumatol"},{"issue":"7","key":"317_CR14","doi-asserted-by":"publisher","first-page":"2096","DOI":"10.1002\/art.21930","volume":"54","author":"A Filer","year":"2006","unstructured":"Filer A, Parsonage G, Smith E, Osborne C, Thomas AM, Curnow SJ, Rainger GE, Raza K, Nash GB, Lord J, et al. Differential survival of leukocyte subsets mediated by synovial, bone marrow, and skin fibroblasts: site-specific versus activation-dependent survival of T cells and neutrophils. Arthritis Rheum. 2006;54(7):2096\u2013108.","journal-title":"Arthritis Rheum"},{"issue":"1","key":"317_CR15","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1002\/eji.200838232","volume":"39","author":"HM McGettrick","year":"2009","unstructured":"McGettrick HM, Smith E, Filer A, Kissane S, Salmon M, Buckley CD, Rainger GE, Nash GB. Fibroblasts from different sites may promote or inhibit recruitment of flowing lymphocytes by endothelial cells. Eur J Immunol. 2009;39(1):113\u201325.","journal-title":"Eur J Immunol"},{"issue":"10","key":"317_CR16","doi-asserted-by":"publisher","first-page":"2926","DOI":"10.1002\/art.24844","volume":"60","author":"MJ del Rey","year":"2009","unstructured":"del Rey MJ, Izquierdo E, Caja S, Usategui A, Santiago B, Galindo M, Pablos JL. Human inflammatory synovial fibroblasts induce enhanced myeloid cell recruitment and angiogenesis through a hypoxia-inducible transcription factor 1alpha\/vascular endothelial growth factor-mediated pathway in immunodeficient mice. Arthritis Rheum. 2009;60(10):2926\u201334.","journal-title":"Arthritis Rheum"},{"issue":"10055","key":"317_CR17","doi-asserted-by":"publisher","first-page":"2023","DOI":"10.1016\/S0140-6736(16)30173-8","volume":"388","author":"JS Smolen","year":"2016","unstructured":"Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet. 2016;388(10055):2023\u201338.","journal-title":"Lancet"},{"issue":"3","key":"317_CR18","doi-asserted-by":"publisher","first-page":"899","DOI":"10.4049\/jimmunol.1600502","volume":"197","author":"RS McMahan","year":"2016","unstructured":"McMahan RS, Birkland TP, Smigiel KS, Vandivort TC, Rohani MG, Manicone AM, McGuire JK, Gharib SA, Parks WC. Stromelysin-2 (MMP10) moderates inflammation by controlling macrophage activation. J Immunol. 2016;197(3):899\u2013909.","journal-title":"J Immunol"},{"issue":"3","key":"317_CR19","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1038\/ni.1699","volume":"10","author":"S Hao","year":"2009","unstructured":"Hao S, Baltimore D. The stability of mRNA influences the temporal order of the induction of genes encoding inflammatory molecules. Nat Immunol. 2009;10(3):281\u20138.","journal-title":"Nat Immunol"},{"issue":"6","key":"317_CR20","doi-asserted-by":"publisher","first-page":"2240","DOI":"10.1073\/pnas.1219192110","volume":"110","author":"MT Paulsen","year":"2013","unstructured":"Paulsen MT, Veloso A, Prasad J, Bedi K, Ljungman EA, Tsan YC, Chang CW, Tarrier B, Washburn JG, Lyons R, et al. Coordinated regulation of synthesis and stability of RNA during the acute TNF-induced proinflammatory response. Proc Natl Acad Sci U S A. 2013;110(6):2240\u20135.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7","key":"317_CR21","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0179762","volume":"12","author":"K Loupasakis","year":"2017","unstructured":"Loupasakis K, Kuo D, Sokhi UK, Sohn C, Syracuse B, Giannopoulou EG, Park SH, Kang H, Ratsch G, Ivashkiv LB, et al. Tumor necrosis factor dynamically regulates the mRNA stabilome in rheumatoid arthritis fibroblast-like synoviocytes. PLoS One. 2017;12(7):e0179762.","journal-title":"PLoS One"},{"issue":"1","key":"317_CR22","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1002\/art.38871","volume":"67","author":"C Sohn","year":"2015","unstructured":"Sohn C, Lee A, Qiao Y, Loupasakis K, Ivashkiv LB, Kalliolias GD. Prolonged tumor necrosis factor alpha primes fibroblast-like synoviocytes in a gene-specific manner by altering chromatin. Arthritis Rheumatol. 2015;67(1):86\u201395.","journal-title":"Arthritis Rheumatol"},{"issue":"3","key":"317_CR23","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1136\/ard.2011.150284","volume":"71","author":"S Rosengren","year":"2012","unstructured":"Rosengren S, Corr M, Firestein GS, Boyle DL. The JAK inhibitor CP-690,550 (tofacitinib) inhibits TNF-induced chemokine expression in fibroblast-like synoviocytes: autocrine role of type I interferon. Ann Rheum Dis. 2012;71(3):440\u20137.","journal-title":"Ann Rheum Dis"},{"issue":"9","key":"317_CR24","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1016\/S0167-5699(97)01103-1","volume":"18","author":"H Tilg","year":"1997","unstructured":"Tilg H, Dinarello CA, Mier JW. IL-6 and APPs: anti-inflammatory and immunosuppressive mediators. Immunol Today. 1997;18(9):428\u201332.","journal-title":"Immunol Today"},{"issue":"5","key":"317_CR25","first-page":"1097","volume":"138","author":"TR Ulich","year":"1991","unstructured":"Ulich TR, Yin S, Guo K, Yi ES, Remick D, del Castillo J. Intratracheal injection of endotoxin and cytokines. II. Interleukin-6 and transforming growth factor beta inhibit acute inflammation. Am J Pathol. 1991;138(5):1097\u2013101.","journal-title":"Am J Pathol"},{"issue":"6","key":"317_CR26","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1016\/S1074-7613(01)00151-0","volume":"14","author":"SM Hurst","year":"2001","unstructured":"Hurst SM, Wilkinson TS, McLoughlin RM, Jones S, Horiuchi S, Yamamoto N, Rose-John S, Fuller GM, Topley N, Jones SA. Il-6 and its soluble receptor orchestrate a temporal switch in the pattern of leukocyte recruitment seen during acute inflammation. Immunity. 2001;14(6):705\u201314.","journal-title":"Immunity"},{"issue":"1","key":"317_CR27","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/S1471-4906(02)00013-3","volume":"24","author":"G Kaplanski","year":"2003","unstructured":"Kaplanski G, Marin V, Montero-Julian F, Mantovani A, Farnarier C. IL-6: a regulator of the transition from neutrophil to monocyte recruitment during inflammation. Trends Immunol. 2003;24(1):25\u20139.","journal-title":"Trends Immunol"},{"issue":"5","key":"317_CR28","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1517\/14728222.11.5.613","volume":"11","author":"S Rose-John","year":"2007","unstructured":"Rose-John S, Waetzig GH, Scheller J, Grotzinger J, Seegert D. The IL-6\/sIL-6R complex as a novel target for therapeutic approaches. Expert Opin Ther Targets. 2007;11(5):613\u201324.","journal-title":"Expert Opin Ther Targets"},{"issue":"1","key":"317_CR29","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1096\/fj.99-1003rev","volume":"15","author":"SA Jones","year":"2001","unstructured":"Jones SA, Horiuchi S, Topley N, Yamamoto N, Fuller GM. The soluble interleukin 6 receptor: mechanisms of production and implications in disease. FASEB J. 2001;15(1):43\u201358.","journal-title":"FASEB J"},{"issue":"3","key":"317_CR30","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1084\/jem.189.3.599","volume":"189","author":"SA Jones","year":"1999","unstructured":"Jones SA, Novick D, Horiuchi S, Yamamoto N, Szalai AJ, Fuller GM. C-reactive protein: a physiological activator of interleukin 6 receptor shedding. J Exp Med. 1999;189(3):599\u2013604.","journal-title":"J Exp Med"},{"issue":"6","key":"317_CR31","doi-asserted-by":"publisher","first-page":"3435","DOI":"10.4049\/jimmunol.167.6.3435","volume":"167","author":"V Marin","year":"2001","unstructured":"Marin V, Montero-Julian FA, Gres S, Boulay V, Bongrand P, Farnarier C, Kaplanski G. The IL-6-soluble IL-6Ralpha autocrine loop of endothelial activation as an intermediate between acute and chronic inflammation: an experimental model involving thrombin. J Immunol. 2001;167(6):3435\u201342.","journal-title":"J Immunol"},{"issue":"11","key":"317_CR32","doi-asserted-by":"publisher","first-page":"2752","DOI":"10.1172\/JCI119821","volume":"100","author":"V Modur","year":"1997","unstructured":"Modur V, Li Y, Zimmerman GA, Prescott SM, McIntyre TM. Retrograde inflammatory signaling from neutrophils to endothelial cells by soluble interleukin-6 receptor alpha. J Clin Invest. 1997;100(11):2752\u20136.","journal-title":"J Clin Invest"},{"issue":"3","key":"317_CR33","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/S0167-4889(02)00319-1","volume":"1592","author":"SA Jones","year":"2002","unstructured":"Jones SA, Rose-John S. The role of soluble receptors in cytokine biology: the agonistic properties of the sIL-6R\/IL-6 complex. Biochim Biophys Acta. 2002;1592(3):251\u201363.","journal-title":"Biochim Biophys Acta"},{"issue":"3","key":"317_CR34","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/S1074-7613(00)80334-9","volume":"6","author":"M Romano","year":"1997","unstructured":"Romano M, Sironi M, Toniatti C, Polentarutti N, Fruscella P, Ghezzi P, Faggioni R, Luini W, van Hinsbergh V, Sozzani S, et al. Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment. Immunity. 1997;6(3):315\u201325.","journal-title":"Immunity"},{"issue":"15","key":"317_CR35","doi-asserted-by":"publisher","first-page":"1799","DOI":"10.1161\/01.CIR.101.15.1799","volume":"101","author":"M Klouche","year":"2000","unstructured":"Klouche M, Rose-John S, Schmiedt W, Bhakdi S. Enzymatically degraded, nonoxidized LDL induces human vascular smooth muscle cell activation, foam cell transformation, and proliferation. Circulation. 2000;101(15):1799\u2013805.","journal-title":"Circulation"},{"issue":"1","key":"317_CR36","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1006\/excr.2001.5300","volume":"269","author":"T Matsumiya","year":"2001","unstructured":"Matsumiya T, Imaizumi T, Fujimoto K, Cui X, Shibata T, Tamo W, Kumagai M, Tanji K, Yoshida H, Kimura H, et al. Soluble interleukin-6 receptor alpha inhibits the cytokine-induced fractalkine\/CX3CL1 expression in human vascular endothelial cells in culture. Exp Cell Res. 2001;269(1):35\u201341.","journal-title":"Exp Cell Res"},{"issue":"9","key":"317_CR37","doi-asserted-by":"crossref","first-page":"4992","DOI":"10.4049\/jimmunol.161.9.4992","volume":"161","author":"JW Oh","year":"1998","unstructured":"Oh JW, Van Wagoner NJ, Rose-John S, Benveniste EN. Role of IL-6 and the soluble IL-6 receptor in inhibition of VCAM-1 gene expression. J Immunol. 1998;161(9):4992\u20139.","journal-title":"J Immunol"},{"issue":"6","key":"317_CR38","doi-asserted-by":"publisher","first-page":"3463","DOI":"10.4049\/jimmunol.175.6.3463","volume":"175","author":"SA Jones","year":"2005","unstructured":"Jones SA. Directing transition from innate to acquired immunity: defining a role for IL-6. J Immunol. 2005;175(6):3463\u20138.","journal-title":"J Immunol"},{"issue":"3","key":"317_CR39","doi-asserted-by":"publisher","first-page":"1601","DOI":"10.4049\/jimmunol.167.3.1601","volume":"167","author":"BT Wipke","year":"2001","unstructured":"Wipke BT, Allen PM. Essential role of neutrophils in the initiation and progression of a murine model of rheumatoid arthritis. J Immunol. 2001;167(3):1601\u20138.","journal-title":"J Immunol"},{"issue":"7","key":"317_CR40","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1038\/nri846","volume":"2","author":"RM Pope","year":"2002","unstructured":"Pope RM. Apoptosis as a therapeutic tool in rheumatoid arthritis. Nat Rev Immunol. 2002;2(7):527\u201335.","journal-title":"Nat Rev Immunol"},{"issue":"5","key":"317_CR41","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1002\/art.39563","volume":"68","author":"Y Araki","year":"2016","unstructured":"Araki Y, Tsuzuki Wada T, Aizaki Y, Sato K, Yokota K, Fujimoto K, Kim YT, Oda H, Kurokawa R, Mimura T. Histone methylation and STAT-3 differentially regulate Interleukin-6-induced matrix metalloproteinase gene activation in rheumatoid arthritis synovial fibroblasts. Arthritis Rheumatol. 2016;68(5):1111\u201323.","journal-title":"Arthritis Rheumatol"},{"issue":"5","key":"317_CR42","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1053\/berh.2001.0195","volume":"15","author":"J Martel-Pelletier","year":"2001","unstructured":"Martel-Pelletier J, Welsch DJ, Pelletier JP. Metalloproteases and inhibitors in arthritic diseases. Best Pract Res Clin Rheumatol. 2001;15(5):805\u201329.","journal-title":"Best Pract Res Clin Rheumatol"},{"issue":"1","key":"317_CR43","doi-asserted-by":"publisher","first-page":"8526","DOI":"10.1038\/s41598-017-08581-y","volume":"7","author":"SJ Cutler","year":"2017","unstructured":"Cutler SJ, Doecke JD, Ghazawi I, Yang J, Griffiths LR, Spring KJ, Ralph SJ, Mellick AS. Novel STAT binding elements mediate IL-6 regulation of MMP-1 and MMP-3. Sci Rep. 2017;7(1):8526.","journal-title":"Sci Rep"},{"issue":"24","key":"317_CR44","doi-asserted-by":"publisher","first-page":"6456","DOI":"10.1111\/j.1742-4658.2007.06163.x","volume":"274","author":"X Zhao","year":"2007","unstructured":"Zhao X, Nozell S, Ma Z, Benveniste EN. The interferon-stimulated gene factor 3 complex mediates the inhibitory effect of interferon-beta on matrix metalloproteinase-9 expression. FEBS J. 2007;274(24):6456\u201368.","journal-title":"FEBS J"},{"issue":"12","key":"317_CR45","doi-asserted-by":"publisher","first-page":"5640","DOI":"10.1128\/IAI.00799-07","volume":"75","author":"SY Kassim","year":"2007","unstructured":"Kassim SY, Gharib SA, Mecham BH, Birkland TP, Parks WC, McGuire JK. Individual matrix metalloproteinases control distinct transcriptional responses in airway epithelial cells infected with Pseudomonas aeruginosa. Infect Immun. 2007;75(12):5640\u201350.","journal-title":"Infect Immun"},{"issue":"12","key":"317_CR46","doi-asserted-by":"publisher","first-page":"1749","DOI":"10.1038\/labinvest.2012.141","volume":"92","author":"FL Koller","year":"2012","unstructured":"Koller FL, Dozier EA, Nam KT, Swee M, Birkland TP, Parks WC, Fingleton B. Lack of MMP10 exacerbates experimental colitis and promotes development of inflammation-associated colonic dysplasia. Lab Investig. 2012;92(12):1749\u201359.","journal-title":"Lab Investig"}],"container-title":["BMC Molecular and Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12860-020-00317-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12860-020-00317-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12860-020-00317-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T19:37:07Z","timestamp":1696966627000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcmolcellbiol.biomedcentral.com\/articles\/10.1186\/s12860-020-00317-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,30]]},"references-count":46,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["317"],"URL":"https:\/\/doi.org\/10.1186\/s12860-020-00317-7","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-32228\/v2","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.3.rs-32228\/v1","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.3.rs-32228\/v3","asserted-by":"object"}]},"ISSN":["2661-8850"],"issn-type":[{"value":"2661-8850","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,30]]},"assertion":[{"value":"27 May 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 October 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 October 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study was approved by the Ethics Committee of Hospital 12 de Octubre, Madrid, Spain (N\u00b0 CEI:17\/085). All patients signed a written informed consent.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"AV is currently working as editor at Springer Healthcare Iberica SL, Madrid, Spain. All other authors declare no competing financial interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"74"}}