{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:23:37Z","timestamp":1792034617457,"version":"4.4.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2019,6,6]],"date-time":"2019-06-06T00:00:00Z","timestamp":1559779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"IHU Opera"},{"DOI":"10.13039\/501100004795","name":"Institut Universitaire de France","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004795","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009950","name":"Ministry of Education","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009950","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Hepatic stellate cells (HSCs) have a central role in liver inflammation and fibrosis by producing inflammatory and fibrotic mediators. Their activation is regulated through direct cell\u2013cell interactions, but also through systemic and local effects of soluble factors such as cytokines. The effects of the proinflammatory cytokines interleukin (IL)-17 and tumor necrosis factor (TNF)-\u03b1 and cell interactions with hepatocytes on HSC activation were assessed. Human HSC and HepaRG cells were exposed to IL-17 and\/or TNF-\u03b1. IL-17 and TNF-\u03b1 contribution from immune cells was determined in a co-culture model with phytohemagglutinin (PHA)-activated peripheral blood mononuclear cells (PBMC), HSC and\/or hepatocytes. IL-17 enhanced TNF-\u03b1 effects on the induction of IL-6, IL-1\u03b2, and the chemokine IL-8, chemokine (C-C motif) ligand 20 (CCL20) and monocyte chemoattractant protein-1 (MCP-1) expression\/secretion in isolated HSC cultures. HSC\u2013hepatocyte interactions did not enhance IL-6, IL-8 and CCL20 production compared to hepatocyte alone. However, HSC\u2013hepatocyte interactions increased C-reactive protein expression. IL-17 and\/or TNF-\u03b1 had no direct profibrotic effects on collagen 1 \u03b11, tissue inhibitor of matrix metalloproteinase (TIMP) and matrix metalloproteinase (MMP) 2 gene expression, whereas mRNA levels of MMP3, an enzyme involved in matrix destruction, were up-regulated in HSCs. The use of specific inhibitors of IL-17 and TNF-\u03b1 indicated their contribution to the strong increase of IL-6 and IL-8 production induced by PBMC, HSC and\/or hepatocyte interactions. As chronic liver inflammation leads to liver fibrosis, IL-17 and\/or TNF-\u03b1 neutralization can be of interest to control liver inflammation and therefore its effects on fibrosis.<\/jats:p>","DOI":"10.1111\/cei.13316","type":"journal-article","created":{"date-parts":[[2019,5,18]],"date-time":"2019-05-18T19:39:11Z","timestamp":1558208351000},"page":"111-120","source":"Crossref","is-referenced-by-count":39,"title":["IL-17 and TNF-\u03b1 co-operation contributes to the proinflammatory response of hepatic stellate cells"],"prefix":"10.1093","volume":"198","author":[{"given":"A","family":"Beringer","sequence":"first","affiliation":[{"name":"Immunogenomics and Inflammation research Unit EA 4130, University of Lyon, Lyon, France"},{"name":"Department of Clinical Immunology and Rheumatology, Hospices Civils de Lyon, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3280-6346","authenticated-orcid":false,"given":"P","family":"Miossec","sequence":"additional","affiliation":[{"name":"Immunogenomics and Inflammation research Unit EA 4130, University of Lyon, Lyon, France"},{"name":"Department of Clinical Immunology and Rheumatology, Hospices Civils de Lyon, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,6,6]]},"reference":[{"key":"2022021407182924600_cei13316-bib-0001","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.1158\/0008-5472.CAN-11-3317","article-title":"Hepatocyte\u2013stellate cell crosstalk in the liver engenders a permissive inflammatory microenvironment that drives progression in hepatocellular carcinoma","volume":"72","author":"Coulouarn","year":"2012","journal-title":"Cancer Res"},{"key":"2022021407182924600_cei13316-bib-0002","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.3892\/mmr.2014.2435","article-title":"Rat hepatic stellate cells alter the gene expression profile and promote the growth, migration and invasion of hepatocellular carcinoma cells","volume":"10","author":"Wang","year":"2014","journal-title":"Mol Med Rep"},{"key":"2022021407182924600_cei13316-bib-0003","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1016\/j.autrev.2018.06.008","article-title":"IL-17 and IL-17-producing cells and liver diseases, with focus on autoimmune liver diseases","volume":"17","author":"Beringer","year":"2018","journal-title":"Autoimmun Rev"},{"key":"2022021407182924600_cei13316-bib-0004","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.jss.2013.03.025","article-title":"Interleukin-17A plays a pivotal role in cholestatic liver fibrosis in mice","volume":"183","author":"Hara","year":"2013","journal-title":"J Surg Res"},{"key":"2022021407182924600_cei13316-bib-0005","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1053\/j.gastro.2012.05.049","article-title":"Interleukin-17 signaling in inflammatory, Kupffer cells, and hepatic stellate cells exacerbates liver fibrosis in mice","volume":"143","author":"Meng","year":"2012","journal-title":"Gastroenterology"},{"key":"2022021407182924600_cei13316-bib-0006","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1111\/cei.13140","article-title":"Synergistic effect of interleukin-17 and tumour necrosis factor-\u03b1 on inflammatory response in hepatocytes through interleukin-6-dependent and -independent pathways","volume":"193","author":"Beringer","year":"2018","journal-title":"Clin Exp Immunol"},{"key":"2022021407182924600_cei13316-bib-0007","doi-asserted-by":"crossref","first-page":"3112","DOI":"10.4049\/jimmunol.0801967","article-title":"Genome-wide comparison between IL-17A- and IL-17F-induced effects in human rheumatoid arthritis synoviocytes","volume":"1950","author":"Zrioual","year":"2009","journal-title":"J Immunol (Balt)"},{"key":"2022021407182924600_cei13316-bib-0008","doi-asserted-by":"crossref","first-page":"2176","DOI":"10.1002\/1529-0131(200109)44:9<2176::AID-ART371>3.0.CO;2-4","article-title":"Interleukin-17 enhances tumor necrosis factor alpha-induced synthesis of interleukins 1,6, and 8 in skin and synovial fibroblasts: a possible role as a \u201cfine-tuning cytokine\u201d in inflammation processes","volume":"44","author":"Katz","year":"2001","journal-title":"Arthritis Rheum"},{"key":"2022021407182924600_cei13316-bib-0009","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.molmed.2016.01.001","article-title":"IL-17 in chronic inflammation: from discovery to targeting","volume":"22","author":"Beringer","year":"2016","journal-title":"Trends Mol Med"},{"key":"2022021407182924600_cei13316-bib-0010","doi-asserted-by":"crossref","first-page":"1753","DOI":"10.1016\/j.tiv.2015.07.010","article-title":"The interplay between hepatic stellate cells and hepatocytes in an in vitro model of NASH","volume":"29","author":"Barbero-Becerra","year":"2015","journal-title":"Toxicol in Vitro Int"},{"key":"2022021407182924600_cei13316-bib-0011","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1471-230X-13-17","article-title":"Co-culture of primary human tumor hepatocytes from patients with hepatocellular carcinoma with autologous peripheral blood mononuclear cells: study of their in vitro immunological interactions","volume":"13","author":"Doumba","year":"2013","journal-title":"BMC Gastroenterol"},{"key":"2022021407182924600_cei13316-bib-0012","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1136\/annrheumdis-2011-200468","article-title":"Combination of IL-17 and TNF\u03b1 induces a pro-inflammatory, pro-coagulant and pro-thrombotic phenotype in human endothelial cells","volume":"71","author":"Hot","year":"2012","journal-title":"Ann Rheum Dis"},{"key":"2022021407182924600_cei13316-bib-0013","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1016\/j.jhep.2016.02.004","article-title":"IL-6 pathway in the liver: from physiopathology to therapy","volume":"64","author":"Schmidt-Arras","year":"2016","journal-title":"J. Hepatol"},{"key":"2022021407182924600_cei13316-bib-0014","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/1478-811X-8-19","article-title":"Interleukin-27 acts on hepatic stellate cells and induces signal transducer and activator of transcription 1-dependent responses","volume":"8","author":"Schoenherr","year":"2010","journal-title":"Cell Commun Signal"},{"key":"2022021407182924600_cei13316-bib-0015","doi-asserted-by":"crossref","first-page":"3925","DOI":"10.4049\/jimmunol.1400861","article-title":"IL-17A enhances the expression of profibrotic genes through upregulation of the TGF-\u03b2 receptor on hepatic stellate cells in a JNK-dependent manner","volume":"1950","author":"Fabre","year":"2014","journal-title":"J Immunol (Balt)"},{"key":"2022021407182924600_cei13316-bib-0016","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/j.1478-3231.2009.02161.x","article-title":"Hepatocarcinoma cells stimulate the growth, migration and expression of pro-angiogenic genes in human hepatic stellate cells","volume":"30","author":"Sancho-Bru","year":"2010","journal-title":"Liver Int"},{"key":"2022021407182924600_cei13316-bib-0017","doi-asserted-by":"crossref","first-page":"R143","DOI":"10.1186\/ar3085","article-title":"Rare incidence of methotrexate-specific lesions in liver biopsy of patients with arthritis and elevated liver enzymes","volume":"12","author":"Quintin","year":"2010","journal-title":"Arthritis Res Ther"},{"key":"2022021407182924600_cei13316-bib-0018","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1136\/gut.2004.042127","article-title":"Human hepatic stellate cell lines, LX-1 and LX-2: new tools for analysis of hepatic fibrosis","volume":"54","author":"Xu","year":"2005","journal-title":"Gut"},{"key":"2022021407182924600_cei13316-bib-0019","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1111\/j.1582-4934.2007.00060.x","article-title":"Immortal hepatic stellate cell lines: useful tools to study hepatic stellate cell biology and function?","volume":"11","author":"Herrmann","year":"2007","journal-title":"J Cell Mol Med"},{"key":"2022021407182924600_cei13316-bib-0020","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1111\/j.1365-2893.2011.01561.x","article-title":"Increased Th17 cells contribute to disease progression in patients with HBV-associated liver cirrhosis","volume":"19","author":"Sun","year":"2012","journal-title":"J Viral Hepatol"},{"key":"2022021407182924600_cei13316-bib-0021","doi-asserted-by":"crossref","first-page":"e1888","DOI":"10.1097\/MD.0000000000001888","article-title":"The distribution and the fibrotic role of elevated inflammatory Th17 cells in patients with primary biliary cirrhosis","volume":"94","author":"Shi","year":"2015","journal-title":"Medicine (Balt)"},{"key":"2022021407182924600_cei13316-bib-0022","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.4049\/jimmunol.1203013","article-title":"IL-17A plays a critical role in the pathogenesis of liver fibrosis through hepatic stellate cell activation","volume":"1950","author":"Tan","year":"2013","journal-title":"J Immunol (Balt)"},{"key":"2022021407182924600_cei13316-bib-0023","doi-asserted-by":"crossref","first-page":"eaar7754","DOI":"10.1126\/sciimmunol.aar7754","article-title":"Type 3 cytokines IL-17A and IL-22 drive TGF-\u03b2-dependent liver fibrosis","volume":"3","author":"Fabre","year":"2018","journal-title":"Sci Immunol"},{"key":"2022021407182924600_cei13316-bib-0024","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1002\/hep.24388","article-title":"Critical role of tumor necrosis factor receptor 1, but not 2, in hepatic stellate cell proliferation, extracellular matrix remodeling, and liver fibrogenesis","volume":"54","author":"Tarrats","year":"2011","journal-title":"Hepatol (Balt)"},{"key":"2022021407182924600_cei13316-bib-0025","doi-asserted-by":"crossref","first-page":"e0153118","DOI":"10.1371\/journal.pone.0153118","article-title":"Characterization of the MMP\/TIMP imbalance and collagen production induced by IL-1\u03b2 or TNF-\u03b1 release from human hepatic stellate cells","volume":"11","author":"Robert","year":"2016","journal-title":"PLOS ONE"},{"key":"2022021407182924600_cei13316-bib-0026","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/S0168-8278(99)80007-5","article-title":"Expression patterns of matrix metalloproteinases and their inhibitors in parenchymal and non-parenchymal cells of rat liver: regulation by TNF-alpha and TGF-beta1","volume":"30","author":"Knittel","year":"1999","journal-title":"J Hepatol"},{"key":"2022021407182924600_cei13316-bib-0027","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3892\/mmr.2015.3429","article-title":"Cluster of differentiation 147 is a key molecule during hepatocellular carcinoma cell-hepatic stellate cell cross-talk in the rat liver","volume":"12","author":"Ma","year":"2015","journal-title":"Mol Med Rep"},{"key":"2022021407182924600_cei13316-bib-0028","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.molimm.2014.10.021","article-title":"Synergistic effect of pro-inflammatory TNF\u03b1 and IL-17 in periostin mediated collagen deposition: potential role in liver fibrosis","volume":"64","author":"Amara","year":"2015","journal-title":"Mol Immunol"},{"key":"2022021407182924600_cei13316-bib-0029","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1002\/hep.22680","article-title":"The interleukin-17 pathway is involved in human alcoholic liver disease","volume":"49","author":"Lemmers","year":"2009","journal-title":"Hepatology (Balt)"},{"key":"2022021407182924600_cei13316-bib-0030","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1002\/hep.29782","article-title":"MAIT cells are chronically activated in patients with autoimmune liver disease and promote profibrogenic hepatic stellate cell activation","volume":"68","author":"B\u00f6ttcher","year":"2018","journal-title":"Hepatol (Balt)"},{"key":"2022021407182924600_cei13316-bib-0031","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1002\/hep.26351","article-title":"C-C motif chemokine receptor 9 positive macrophages activate hepatic stellate cells and promote liver fibrosis in mice","volume":"58","author":"Chu","year":"2013","journal-title":"Hepatology (Balt)"},{"key":"2022021407182924600_cei13316-bib-0032","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1002\/hep.26429","article-title":"Hepatic macrophages but not dendritic cells contribute to liver fibrosis by promoting the survival of activated hepatic stellate cells in mice","volume":"58","author":"Pradere","year":"2013","journal-title":"Hepatology (Balt)"}],"container-title":["Clinical and Experimental Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cei.13316","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cei.13316","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/198\/1\/111\/42507508\/cei13316.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/198\/1\/111\/42507508\/cei13316.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T07:01:17Z","timestamp":1721286077000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cei\/article\/198\/1\/111\/6402596"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,6]]},"references-count":32,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,6,6]]},"published-print":{"date-parts":[[2019,9,2]]}},"URL":"https:\/\/doi.org\/10.1111\/cei.13316","relation":{},"ISSN":["1365-2249","0009-9104"],"issn-type":[{"value":"1365-2249","type":"electronic"},{"value":"0009-9104","type":"print"}],"subject":[],"published-other":{"date-parts":[[2019,10]]},"published":{"date-parts":[[2019,6,6]]}}}