{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T09:33:09Z","timestamp":1778664789579,"version":"3.51.4"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2013,3,11]],"date-time":"2013-03-11T00:00:00Z","timestamp":1362960000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,3,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The CXC chemokines, monokine induced by interferon (IFN)-gamma (MIG) (CXCL9), IFN-gamma-induced protein 10 (IP-10) (CXCL10) and IFN-inducible T cell alpha chemoattractant (I-TAC) (CXCL11), are known to attract CXCR3- (CXCR3A and CXCR3B) T lymphocytes. We investigated MIG, IP-10 and I-TAC mRNAs expression by semi-quantitative multiplex reverse transcription\u2013polymerase chain reaction (RT\u2013PCR) in liver biopsies obtained from patients with a first diagnosis of primary biliary cirrhosis [(PBC)\u2009=\u200920] compared to patients with normal liver biopsy [normal controls (NCs)\u2009=\u200920]. Chemokine production was assessed by enzyme-linked immunosorbent assay (ELISA) in serum. Measurements were repeated 6 months after ursodeoxycholic acid (UDCA) treatment in PBC patients. CXCR3A and CXCR3B mRNAs expression was examined in immunomagnetically sorted CD3+ peripheral blood lymphocytes (PBL) pre- and post-treatment by RT\u2013PCR. Flow cytometry was used to evaluate the expression of CXCR3+ PBLs of NCs and PBC patients. A marked mRNA expression of MIG and IP-10 was found in PBC patients. I-TAC mRNA was not detected. In serum of PBC patients there was a significant increase of MIG and IP-10 compared to NCs. Interestingly, there was a significant reduction of these proteins in patients' serum after UDCA treatment. I-TAC was not statistically different between groups. CXCR3A mRNA expression was found in PBLs from PBC patients as well as in NCs. CXCR3B mRNA was expressed in four of 20 (19%) NCs and 20 of 20 PBC patients. Flow cytometry revealed a significantly lower CXCR3 expression in NCs (13\u00b75%) than in PBC (37\u00b72%), which was reduced (28\u00b71%, P\u2009&amp;lt;\u20090\u00b701) after UDCA administration. These data suggest a possible role for CXCR3-binding chemokines and their receptor in the aetiopathogenetic recruitment of lymphocytes in PBC and a new mechanism of action for UDCA.<\/jats:p>","DOI":"10.1111\/cei.12032","type":"journal-article","created":{"date-parts":[[2012,11,21]],"date-time":"2012-11-21T04:01:51Z","timestamp":1353470511000},"page":"9-15","source":"Crossref","is-referenced-by-count":33,"title":["CXCR3 axis in patients with primary biliary cirrhosis: a possible novel mechanism of the effect of ursodeoxycholic acid"],"prefix":"10.1093","volume":"172","author":[{"given":"P","family":"Manousou","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Liver Research Laboratory, University of Crete, Heraklion, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G","family":"Kolios","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, Faculty of Medicine, Democritus University of Thrace, Alexandroupolis, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I","family":"Drygiannakis","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Liver Research Laboratory, University of Crete, Heraklion, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Koulentaki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Liver Research Laboratory, University of Crete, Heraklion, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Pyrovolaki","sequence":"additional","affiliation":[{"name":"Haematology Research Laboratory, Faculty of Medicine, University of Crete, Heraklion, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Voumvouraki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Liver Research Laboratory, University of Crete, Heraklion, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G","family":"Notas","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Liver Research Laboratory, University of Crete, Heraklion, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L","family":"Bourikas","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Liver Research Laboratory, University of Crete, Heraklion, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H A","family":"Papadaki","sequence":"additional","affiliation":[{"name":"Haematology Research Laboratory, Faculty of Medicine, University of Crete, Heraklion, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E","family":"Kouroumalis","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Liver Research Laboratory, University of Crete, Heraklion, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2013,3,11]]},"reference":[{"key":"2021122009531574400_cei12032-bib-0001","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1034\/j.1600-065X.2000.17703.x","article-title":"The role of chemokines in the immunopathology of the liver","volume":"177","author":"Bone-Larson","year":"2000","journal-title":"Immunol Rev"},{"key":"2021122009531574400_cei12032-bib-0002","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1046\/j.1440-1711.2002.01062.x","article-title":"Recruitment of lymphocytes to the human liver","volume":"80","author":"Lalor","year":"2002","journal-title":"Immunol Cell Biol"},{"key":"2021122009531574400_cei12032-bib-0003","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1084\/jem.187.12.2009","article-title":"Interferon-inducible T cell alpha chemoattractant (I-TAC): a novel non-ELR CXC chemokine with potent activity on activated T cells through selective high affinity binding to CXCR3","volume":"187","author":"Cole","year":"1998","journal-title":"J Exp Med"},{"key":"2021122009531574400_cei12032-bib-0004","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1097\/01.MIB.0000178263.34099.89","article-title":"Anti-interferon-inducible chemokine, CXCL10, reduces colitis by impairing T helper-1 induction and recruitment in mice","volume":"11","author":"Hyun","year":"2005","journal-title":"Inflamm Bowel Dis"},{"key":"2021122009531574400_cei12032-bib-0005","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1002\/(SICI)1521-4141(199803)28:03<961::AID-IMMU961>3.0.CO;2-4","article-title":"The chemokine receptor CXCR3 mediates rapid and shear-resistant adhesion-induction of effector T lymphocytes by the chemokines IP10 and Mig","volume":"28","author":"Piali","year":"1998","journal-title":"Eur J Immunol"},{"key":"2021122009531574400_cei12032-bib-0006","doi-asserted-by":"crossref","first-page":"6234","DOI":"10.4049\/jimmunol.173.10.6234","article-title":"Identification and partial characterization of a variant of human CXCR3 generated by posttranscriptional exon skipping","volume":"173","author":"Ehlert","year":"2004","journal-title":"J Immunol"},{"key":"2021122009531574400_cei12032-bib-0007","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1084\/jem.20021897","article-title":"An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4","volume":"197","author":"Lasagni","year":"2003","journal-title":"J Exp Med"},{"key":"2021122009531574400_cei12032-bib-0008","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s00535-007-2019-y","article-title":"Primary biliary cirrhosis: what we know and what we want to know about human PBC and spontaneous PBC mouse models","volume":"42","author":"Ueno","year":"2007","journal-title":"J Gastroenterol"},{"key":"2021122009531574400_cei12032-bib-0009","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1053\/jhep.2002.36088","article-title":"Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited","volume":"36","author":"Paumgartner","year":"2002","journal-title":"Hepatology"},{"key":"2021122009531574400_cei12032-bib-0010","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/BF00432479","article-title":"Staging of chronic nonsuppurative destructive cholangitis (syndrome of primary biliary cirrhosis)","volume":"379","author":"Ludwig","year":"1978","journal-title":"Virchows Arch A Pathol Anat Histol"},{"key":"2021122009531574400_cei12032-bib-0011","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1007\/s00277-003-0709-y","article-title":"Increased cell apoptosis in bone marrow trephine biopsies and immunomagnetically isolated myeloid progenitor cells in patients with chronic idiopathic neutropenia","volume":"82","author":"Koumaki","year":"2003","journal-title":"Ann Hematol"},{"key":"2021122009531574400_cei12032-bib-0012","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1111\/j.1365-2362.2006.01710.x","article-title":"Ciprofloxacin inhibits cytokine-induced nitric oxide production in human colonic epithelium","volume":"36","author":"Kolios","year":"2006","journal-title":"Eur J Clin Invest"},{"key":"2021122009531574400_cei12032-bib-0013","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1172\/JCI6685","article-title":"Expression of functional CXCR4 chemokine receptors on human colonic epithelial cells","volume":"104","author":"Jordan","year":"1999","journal-title":"J Clin Invest"},{"key":"2021122009531574400_cei12032-bib-0014","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1111\/j.1365-2141.2005.05380.x","article-title":"Activated T-lymphocytes with myelosuppressive properties in patients with chronic idiopathic neutropenia","volume":"128","author":"Papadaki","year":"2005","journal-title":"Br J Haematol"},{"key":"2021122009531574400_cei12032-bib-0015","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.jhep.2007.04.009","article-title":"The role of CCR5\/CXCR3 expressing CD8+ cells in liver damage and viral control during persistent hepatitis C virus infection","volume":"47","author":"Larrubia","year":"2007","journal-title":"J Hepatol"},{"key":"2021122009531574400_cei12032-bib-0016","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.jaut.2005.08.009","article-title":"Increased levels of chemokine receptor CXCR3 and chemokines IP-10 and MIG in patients with primary biliary cirrhosis and their first degree relatives","volume":"25","author":"Chuang","year":"2005","journal-title":"J Autoimmun"},{"key":"2021122009531574400_cei12032-bib-0017","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1016\/j.jhep.2012.07.008","article-title":"CXCR3-dependent recruitment and CCR6-mediated positioning of Th-17 cells in the inflamed liver","volume":"57","author":"Oo","year":"2012","journal-title":"J Hepatol"},{"key":"2021122009531574400_cei12032-bib-0018","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1002\/hep.21123","article-title":"Liver-targeted and peripheral blood alterations of regulatory T cells in primary biliary cirrhosis","volume":"43","author":"Lan","year":"2006","journal-title":"Hepatology"},{"key":"2021122009531574400_cei12032-bib-0019","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1002\/hep.22651","article-title":"Deficiency in regulatory T cells results in development of antimitochondrial antibodies and autoimmune cholangitis","volume":"49","author":"Zhang","year":"2009","journal-title":"Hepatology"},{"key":"2021122009531574400_cei12032-bib-0020","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1002\/hep.22761","article-title":"Natural killer T cells regulate the homing of chemokine CXC receptor 3-positive regulatory T cells to the liver in mice","volume":"49","author":"Santodomingo-Garzon","year":"2009","journal-title":"Hepatology"},{"key":"2021122009531574400_cei12032-bib-0021","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.jaut.2010.09.003","article-title":"CXCL10 promotes liver fibrosis by prevention of NK cell mediated hepatic stellate cell inactivation","volume":"35","author":"Hintermann","year":"2010","journal-title":"J Autoimmun"},{"key":"2021122009531574400_cei12032-bib-0022","doi-asserted-by":"crossref","first-page":"5284","DOI":"10.4049\/jimmunol.1003750","article-title":"CXCR3 deficiency exacerbates liver disease and abrogates tolerance in a mouse model of immune-mediated hepatitis","volume":"186","author":"Erhardt","year":"2011","journal-title":"J Immunol"},{"key":"2021122009531574400_cei12032-bib-0023","doi-asserted-by":"crossref","first-page":"2886","DOI":"10.4049\/jimmunol.0901216","article-title":"Distinct roles for CCR4 and CXCR3 in the recruitment and positioning of regulatory T cells in the inflamed human liver","volume":"184","author":"Oo","year":"2010","journal-title":"J Immunol"},{"key":"2021122009531574400_cei12032-bib-0024","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1172\/JCI6993","article-title":"Differential expression of three T lymphocyte-activating CXC chemokines by human atheroma-associated cells","volume":"104","author":"Mach","year":"1999","journal-title":"J Clin Invest"},{"key":"2021122009531574400_cei12032-bib-0025","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1084\/jem.184.3.963","article-title":"Chemokine receptor specific for IP10 and mig: structure, function, and expression in activated T-lymphocytes","volume":"184","author":"Loetscher","year":"1996","journal-title":"J Exp Med"},{"key":"2021122009531574400_cei12032-bib-0026","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1002\/jlb.61.3.246","article-title":"Mig and IP-10: CXC chemokines that target lymphocytes","volume":"61","author":"Farber","year":"1997","journal-title":"J Leukoc Biol"},{"key":"2021122009531574400_cei12032-bib-0027","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1111\/j.1365-2036.2005.02307.x","article-title":"Ursodeoxycholic acid reduces increased circulating endothelin 2 in primary biliary cirrhosis","volume":"21","author":"Dimoulios","year":"2005","journal-title":"Aliment Pharmacol Ther"},{"key":"2021122009531574400_cei12032-bib-0028","doi-asserted-by":"crossref","first-page":"6236","DOI":"10.4049\/jimmunol.163.11.6236","article-title":"Chemokine and chemokine receptor interactions provide a mechanism for selective T cell recruitment to specific liver compartments within hepatitis C-infected liver","volume":"163","author":"Shields","year":"1999","journal-title":"J Immunol"},{"key":"2021122009531574400_cei12032-bib-0029","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.tox.2008.08.003","article-title":"Lymphocyte recruitment to the liver: molecular insights into the pathogenesis of liver injury and hepatitis","volume":"254","author":"Shetty","year":"2008","journal-title":"Toxicology"},{"key":"2021122009531574400_cei12032-bib-0030","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1053\/j.gastro.2008.10.020","article-title":"Liver myofibroblasts regulate infiltration and positioning of lymphocytes in human liver","volume":"136","author":"Holt","year":"2009","journal-title":"Gastroenterology"},{"key":"2021122009531574400_cei12032-bib-0031","doi-asserted-by":"crossref","first-page":"2320","DOI":"10.3748\/wjg.v12.i15.2320","article-title":"Pathogenesis of primary biliary cirrhosis: a unifying model","volume":"12","author":"Kouroumalis","year":"2006","journal-title":"World J Gastroenterol"},{"key":"2021122009531574400_cei12032-bib-0032","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1002\/hep.22443","article-title":"Enhanced T cell transmigration across the murine liver sinusoidal endothelium is mediated by transcytosis and surface presentation of chemokines","volume":"48","author":"Schrage","year":"2008","journal-title":"Hepatology"},{"key":"2021122009531574400_cei12032-bib-0033","first-page":"372","article-title":"Promotion of leukocyte transendothelial cell migration by chemokines derived from human biliary epithelial cells in vitro","volume":"109","author":"Morland","year":"1997","journal-title":"Proc Assoc Am Physicians"},{"key":"2021122009531574400_cei12032-bib-0034","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1172\/JCI6642","article-title":"Active participation of CCR5(+)CD8(+) T lymphocytes in the pathogenesis of liver injury in graft-versus-host disease","volume":"104","author":"Murai","year":"1999","journal-title":"J Clin Invest"}],"container-title":["Clinical and Experimental Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcei.12032","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/172\/1\/9\/41788256\/cei12032.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/172\/1\/9\/41788256\/cei12032.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T22:08:53Z","timestamp":1687817333000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cei\/article\/172\/1\/9\/6421054"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,3,11]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2013,3,11]]},"published-print":{"date-parts":[[2013,3,11]]}},"URL":"https:\/\/doi.org\/10.1111\/cei.12032","relation":{},"ISSN":["1365-2249","0009-9104"],"issn-type":[{"value":"1365-2249","type":"electronic"},{"value":"0009-9104","type":"print"}],"subject":[],"published-other":{"date-parts":[[2013,4]]},"published":{"date-parts":[[2013,3,11]]}}}