{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:46:28Z","timestamp":1784335588824,"version":"3.55.0"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2013,2,28]],"date-time":"2013-02-28T00:00:00Z","timestamp":1362009600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Diagn Pathol"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background\/objectives<\/jats:title><jats:p>As a proinflammatory cytokine, interleukin-17 (IL-17) contributes to the inflammation of many autoimmune diseases. We examined IL-17 levels in serum and tissues from patients with chronic hepatitis B virus infection (HBV), and especially evaluated the role of IL-17 in the pathogenesis and progression of liver fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>Whole venous blood was obtained from four patient groups: chronic hepatitis B (CHB, n\u2009=\u200947), liver cirrhosis (LC, n\u2009=\u200949), primary hepatocellular carcinoma (PHC, n\u2009=\u200944), chronic liver failure (CLF, n\u2009=\u200933), and a normal control group (n\u2009=\u200920). HBsAg was positive in all patients. Liver biopsy samples were acquired from asymptomatic HBsAg carriers (ASC, n\u2009=\u200935), CHB (n\u2009=\u200957), and LC (n\u2009=\u200931) patients. We performed ELISA to measure IL-17 levels in serum samples, and used reverse RT-PCR to measure IL-17 mRNA levels in peripheral blood mononuclear cells (PBMC). IL-17 protein expression was detected in liver biopsy tissues by immunohistochemistry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to normal controls, serum IL-17 protein and mRNA levels were significantly higher in the four infection groups. LC patients exhibited the highest serum IL-17 and PBMC mRNA levels. No significant differences were found between the other three groups. High levels of IL-17 were also observed in tissues from CHB and LC patients, compared to ASC. IL-17 expression was mainly located in the portal area and was positively correlated with inflammation grade and fibrosis stage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>IL-17 expression was found to be increased with increasing degrees of liver fibrosis. This suggests that IL-17 may not only induce the inflammation, but also contribute to disease progression and chronicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Virtual Slides<\/jats:title><jats:p>The virtual slide(s) for this article can be found here:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.diagnosticpathology.diagnomx.eu\/vs\/5306959258322482\" ext-link-type=\"uri\">http:\/\/www.diagnosticpathology.diagnomx.eu\/vs\/5306959258322482<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1186\/1746-1596-8-40","type":"journal-article","created":{"date-parts":[[2013,2,28]],"date-time":"2013-02-28T17:09:29Z","timestamp":1362071369000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Expression of Interleukin-17 associated with disease progression and liver fibrosis with hepatitis B virus infection: IL-17 in HBV infection"],"prefix":"10.1186","volume":"8","author":[{"given":"Wen-Jun","family":"Du","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Hui","family":"Zhen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao-Qing","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao-Min","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lai-Ying","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-Jun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,2,28]]},"reference":[{"issue":"11","key":"712_CR1","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1038\/ni1254","volume":"6","author":"LE Harrington","year":"2005","unstructured":"Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, Weaver CT: Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol. 2005, 6 (11): 1123-1132. 10.1038\/ni1254.","journal-title":"Nat Immunol"},{"key":"712_CR2","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/1746-1596-7-103","volume":"7","author":"AA Mohamed","year":"2012","unstructured":"Mohamed AA, Nada OH, El Desouky MA: Implication of protein kinase R gene quantification in hepatitis C virus genotype 4 induced hepatocarcinogenesis. Diagn Pathol. 2012, 7: 103-10.1186\/1746-1596-7-103.","journal-title":"Diagn Pathol"},{"key":"712_CR3","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1186\/1746-1596-7-142","volume":"7","author":"H Xu","year":"2012","unstructured":"Xu H, Cao D, Guo G, Ruan Z, Wu Y, Chen Y: The intrahepatic expression and distribution of BTLA and its ligand HVEM in patients with HBV-related acute-on-chronic liver failure. Diagn Pathol. 2012, 7: 142-10.1186\/1746-1596-7-142.","journal-title":"Diagn Pathol"},{"issue":"3","key":"712_CR4","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1183\/09031936.02.00280902","volume":"19","author":"M Laan","year":"2002","unstructured":"Laan M, Palmberg L, Larsson K, Linden A: Free, soluble interleukin-17 protein during severe inflammation in human airways. Eur Respir J. 2002, 19 (3): 534-537. 10.1183\/09031936.02.00280902.","journal-title":"Eur Respir J"},{"issue":"6","key":"712_CR5","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1067\/mai.2003.1557","volume":"111","author":"J Chakir","year":"2003","unstructured":"Chakir J, Shannon J, Molet S, Fukakusa M, Elias J, Laviolette M, Boulet LP, Hamid Q: Airway remodeling-associated mediators in moderate to severe asthma: effect of steroids on TGF-beta, IL-11, IL-17, and type I and type III collagen expression. J Allergy Clin Immunol. 2003, 111 (6): 1293-1298. 10.1067\/mai.2003.1557.","journal-title":"J Allergy Clin Immunol"},{"issue":"3","key":"712_CR6","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1186\/ar294","volume":"3","author":"M Chabaud","year":"2001","unstructured":"Chabaud M, Lubberts E, Joosten L, van Den Berg W, Miossec P: IL-17 derived from juxta-articular bone and synovium contributes to joint degradation in rheumatoid arthritis. Arthritis Res. 2001, 3 (3): 168-177. 10.1186\/ar294.","journal-title":"Arthritis Res"},{"issue":"1","key":"712_CR7","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1136\/gut.52.1.65","volume":"52","author":"S Fujino","year":"2003","unstructured":"Fujino S, Andoh A, Bamba S, Ogawa A, Hata K, Araki Y, Bamba T, Fujiyama Y: Increased expression of interleukin 17 in inflammatory bowel disease. Gut. 2003, 52 (1): 65-70. 10.1136\/gut.52.1.65.","journal-title":"Gut"},{"issue":"2","key":"712_CR8","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.immuni.2006.01.001","volume":"24","author":"M Veldhoen","year":"2006","unstructured":"Veldhoen M, Hocking RJ, Atkins CJ, Locksley RM, Stockinger B: TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity. 2006, 24 (2): 179-189. 10.1016\/j.immuni.2006.01.001.","journal-title":"Immunity"},{"issue":"42","key":"712_CR9","doi-asserted-by":"publisher","first-page":"27467","DOI":"10.1074\/jbc.273.42.27467","volume":"273","author":"T Shalom-Barak","year":"1998","unstructured":"Shalom-Barak T, Quach J, Lotz M: Interleukin-17-induced gene expression in articular chondrocytes is associated with activation of mitogen-activated protein kinases and NF-kappaB. J Biol Chem. 1998, 273 (42): 27467-27473. 10.1074\/jbc.273.42.27467.","journal-title":"J Biol Chem"},{"issue":"9","key":"712_CR10","doi-asserted-by":"crossref","first-page":"5337","DOI":"10.4049\/jimmunol.162.9.5337","volume":"162","author":"M Awane","year":"1999","unstructured":"Awane M, Andres PG, Li DJ, Reinecker HC: NF-kappa B-inducing kinase is a common mediator of IL-17-, TNF-alpha-, and IL-1 beta-induced chemokine promoter activation in intestinal epithelial cells. J Immunol. 1999, 162 (9): 5337-5344.","journal-title":"J Immunol"},{"issue":"4","key":"712_CR11","doi-asserted-by":"publisher","first-page":"2559","DOI":"10.1074\/jbc.M308809200","volume":"279","author":"MJ Ruddy","year":"2004","unstructured":"Ruddy MJ, Wong GC, Liu XK, Yamamoto H, Kasayama S, Kirkwood KL, Gaffen SL: Functional cooperation between interleukin-17 and tumor necrosis factor-alpha is mediated by CCAAT\/enhancer-binding protein family members. J Biol Chem. 2004, 279 (4): 2559-2567.","journal-title":"J Biol Chem"},{"issue":"6","key":"712_CR12","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1002\/hep.1840180624","volume":"18","author":"E Roeb","year":"1993","unstructured":"Roeb E, Graeve L, Hoffmann R, Decker K, Edwards DR, Heinrich PC: Regulation of tissue inhibitor of metalloproteinases-1 gene expression by cytokines and dexamethasone in rat hepatocyte primary cultures. Hepatology. 1993, 18 (6): 1437-1442. 10.1002\/hep.1840180624.","journal-title":"Hepatology"},{"issue":"1","key":"712_CR13","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/0016-5085(93)90033-9","volume":"105","author":"A Casini","year":"1993","unstructured":"Casini A, Pinzani M, Milani S, Grappone C, Galli G, Jezequel AM, Schuppan D, Rotella CM, Surrenti C: Regulation of extracellular matrix synthesis by transforming growth factor beta 1 in human fat-storing cells. Gastroenterology. 1993, 105 (1): 245-253.","journal-title":"Gastroenterology"},{"issue":"1","key":"712_CR14","doi-asserted-by":"publisher","first-page":"404","DOI":"10.4049\/jimmunol.175.1.404","volume":"175","author":"F McAllister","year":"2005","unstructured":"McAllister F, Henry A, Kreindler JL, Dubin PJ, Ulrich L, Steele C, Finder JD, Pilewski JM, Carreno BM, Goldman SJ, Pirhonen J, Kolls JK: Role of IL-17A, IL-17\u00a0F, and the IL-17 receptor in regulating growth-related oncogene-alpha and granulocyte colony-stimulating factor in bronchial epithelium: implications for airway inflammation in cystic fibrosis. J Immunol. 2005, 175 (1): 404-412.","journal-title":"J Immunol"},{"issue":"10","key":"712_CR15","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.1097\/00005537-200310000-00027","volume":"113","author":"SM Molet","year":"2003","unstructured":"Molet SM, Hamid QA, Hamilos DL: IL-11 and IL-17 expression in nasal polyps: relationship to collagen deposition and suppression by intranasal fluticasone propionate. Laryngoscope. 2003, 113 (10): 1803-1812.","journal-title":"Laryngoscope"},{"issue":"4","key":"712_CR16","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1067\/mai.2003.1414","volume":"111","author":"M Toda","year":"2003","unstructured":"Toda M, Leung DY, Molet S, Boguniewicz M, Taha R, Christodoulopoulos P, Fukuda T, Elias JA, Hamid QA: Polarized in vivo expression of IL-11 and IL-17 between acute and chronic skin lesions. J Allergy Clin Immunol. 2003, 111 (4): 875-881. 10.1067\/mai.2003.1414.","journal-title":"J Allergy Clin Immunol"},{"issue":"6","key":"712_CR17","doi-asserted-by":"publisher","first-page":"3920","DOI":"10.4049\/jimmunol.175.6.3920","volume":"175","author":"LI Rutitzky","year":"2005","unstructured":"Rutitzky LI, Lopes Da Rosa JR, Stadecker MJ: Severe CD4 T cell-mediated immunopathology in murine schistosomiasis is dependent on IL-12p40 and correlates with high levels of IL-17. J Immunol. 2005, 175 (6): 3920-3926.","journal-title":"J Immunol"},{"issue":"3","key":"712_CR18","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1067\/mai.2001.117929","volume":"108","author":"S Molet","year":"2001","unstructured":"Molet S, Hamid Q, Davoine F, Nutku E, Taha R, Page N, Olivenstein R, Elias J, Chakir J: IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines. J Allergy Clin Immunol. 2001, 108 (3): 430-438. 10.1067\/mai.2001.117929.","journal-title":"J Allergy Clin Immunol"},{"issue":"7","key":"712_CR19","doi-asserted-by":"publisher","first-page":"2620","DOI":"10.1182\/blood-2002-05-1461","volume":"101","author":"M Numasaki","year":"2003","unstructured":"Numasaki M, Fukushi J, Ono M, Narula SK, Zavodny PJ, Kudo T, Robbins PD, Tahara H, Lotze MT: Interleukin-17 promotes angiogenesis and tumor growth. Blood. 2003, 101 (7): 2620-2627. 10.1182\/blood-2002-05-1461.","journal-title":"Blood"},{"issue":"6","key":"712_CR20","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1182\/blood.V99.6.2114","volume":"99","author":"F Benchetrit","year":"2002","unstructured":"Benchetrit F, Ciree A, Vives V, Warnier G, Gey A, Sautes-Fridman C, Fossiez F, Haicheur N, Fridman WH, Tartour E: Interleukin-17 inhibits tumor cell growth by means of a T-cell-dependent mechanism. Blood. 2002, 99 (6): 2114-2121. 10.1182\/blood.V99.6.2114.","journal-title":"Blood"},{"issue":"5887","key":"712_CR21","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1126\/science.1159806","volume":"321","author":"AM Intlekofer","year":"2008","unstructured":"Intlekofer AM, Banerjee A, Takemoto N, Gordon SM, Dejong CS, Shin H, Hunter CA, Wherry EJ, Lindsten T, Reiner SL: Anomalous type 17 response to viral infection by CD8+ T cells lacking T-bet and eomesodermin. Science. 2008, 321 (5887): 408-411. 10.1126\/science.1159806.","journal-title":"Science"},{"issue":"5","key":"712_CR22","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1002\/hep.20184","volume":"39","author":"S Radaeva","year":"2004","unstructured":"Radaeva S, Sun R, Pan HN, Hong F, Gao B: Interleukin 22 (IL-22) plays a protective role in T cell-mediated murine hepatitis: IL-22 is a survival factor for hepatocytes via STAT3 activation. Hepatology. 2004, 39 (5): 1332-1342. 10.1002\/hep.20184.","journal-title":"Hepatology"},{"issue":"4","key":"712_CR23","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1016\/j.immuni.2007.07.023","volume":"27","author":"LA Zenewicz","year":"2007","unstructured":"Zenewicz LA, Yancopoulos GD, Valenzuela DM, Murphy AJ, Karow M, Flavell RA: Interleukin-22 but not interleukin-17 provides protection to hepatocytes during acute liver inflammation. Immunity. 2007, 27 (4): 647-659. 10.1016\/j.immuni.2007.07.023.","journal-title":"Immunity"},{"issue":"2","key":"712_CR24","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1172\/JCI24282","volume":"115","author":"R Bataller","year":"2005","unstructured":"Bataller R, Brenner DA: Liver fibrosis. J Clin Invest. 2005, 115 (2): 209-218.","journal-title":"J Clin Invest"},{"issue":"5","key":"712_CR25","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1007\/s10495-005-1055-4","volume":"10","author":"AM Elsharkawy","year":"2005","unstructured":"Elsharkawy AM, Oakley F, Mann DA: The role and regulation of hepatic stellate cell apoptosis in reversal of liver fibrosis. Apoptosis. 2005, 10 (5): 927-939. 10.1007\/s10495-005-1055-4.","journal-title":"Apoptosis"}],"container-title":["Diagnostic Pathology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1746-1596-8-40.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/1746-1596-8-40\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1746-1596-8-40.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T20:26:43Z","timestamp":1688070403000},"score":1,"resource":{"primary":{"URL":"https:\/\/diagnosticpathology.biomedcentral.com\/articles\/10.1186\/1746-1596-8-40"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,2,28]]},"references-count":25,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,12]]}},"alternative-id":["712"],"URL":"https:\/\/doi.org\/10.1186\/1746-1596-8-40","relation":{},"ISSN":["1746-1596"],"issn-type":[{"value":"1746-1596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,2,28]]},"assertion":[{"value":"24 October 2012","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 February 2013","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 February 2013","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"40"}}