{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T23:47:18Z","timestamp":1791935238021,"version":"4.3.4"},"reference-count":45,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2008,3]]},"abstract":"<jats:p>Autosomal dominant polycystic kidney disease (ADPKD) is a highly prevalent genetic disease that results in cyst formation in kidney and liver. Cytokines and growth factors secreted by the cyst-lining epithelia are positioned to initiate autocrine\/paracrine signaling and promote cyst growth. Comparative analyses of human kidney and liver cyst fluids revealed disparate cytokine\/growth factor profiles. CXCR2 agonists, including IL-8, epithelial neutrophil-activating peptide (ENA-78), growth-related oncogene-\u03b1 (GRO-\u03b1), are potent proliferative agents that were found at high levels in liver but not kidney cyst fluids. Liver cysts are lined by epithelial cells derived from the intrahepatic bile duct (i.e., cholangiocytes). In polarized pkd2(WS25\/\u2212) mouse liver cyst epithelial monolayers, CXCR2 agonists were released both apically and basally, indicating that they may act both on the endothelial and epithelial cells within or lining the cyst wall. IL-8 and human liver cyst fluid induced cell proliferation of HMEC-1 cells, a human microvascular endothelial cell line, and Mz-ChA1 cells, a human cholangiocyte cell model. IL-8 expression can be regulated by specific stresses. Hypoxia and mechanical stretch, two likely stressors acting on the liver cyst epithelia, significantly increased IL-8 secretion and promoter activity. AP-1, c\/EBP, and NF-\u03baB were required but not sufficient to drive the stress-induced increase in IL-8 transcription. An upstream element between \u2212272 and \u22121,481 bp allowed for the stress-induced increase in IL-8 transcription. These studies support the hypothesis that CXCR2 signaling promotes ADPKD liver cyst growth.<\/jats:p>","DOI":"10.1152\/ajpcell.00457.2007","type":"journal-article","created":{"date-parts":[[2008,1,16]],"date-time":"2008-01-16T20:35:03Z","timestamp":1200515703000},"page":"C786-C796","source":"Crossref","is-referenced-by-count":26,"title":["CXCR2 agonists in ADPKD liver cyst fluids promote cell proliferation"],"prefix":"10.1152","volume":"294","author":[{"given":"Claudia R.","family":"Amura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelley S.","family":"Brodsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berenice","family":"Gitomer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"McFann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwendal","family":"Lazennec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew T.","family":"Nichols","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alkesh","family":"Jani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W.","family":"Schrier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Brian Doctor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"crossref","unstructured":"Addison CL\n                      , Daniel TO, Burdick MD, Liu H, Ehlert JE, Xue YY, Buechi L, Walz A, Richmond A, Strieter RM.\n                      The CXC chemokine receptor 2, CXCR2, is the putative receptor for ELR+ CXC chemokine-induced angiogenic activity.\n                      J Immunol\n                      165\n                      : 5269\u20135277, 2000.","DOI":"10.4049\/jimmunol.165.9.5269"},{"key":"R2","doi-asserted-by":"crossref","unstructured":"Ades EW\n                      , Candal FJ, Swerlick RA, George VG, Summers S, Bosse DC, Lawley TJ.\n                      HMEC-1: establishment of an immortalized human microvascular endothelial cell line.\n                      J Invest Dermatol\n                      99\n                      : 683\u2013690, 1992.","DOI":"10.1111\/1523-1747.ep12613748"},{"key":"R3","doi-asserted-by":"crossref","unstructured":"Ali S\n                      , Lazennec G.\n                      Chemokines: novel targets for breast cancer metastasis.\n                      Cancer Metastasis Rev\n                      26\n                      : 401\u2013420, 2007.","DOI":"10.1007\/s10555-007-9073-z"},{"key":"R4","doi-asserted-by":"crossref","unstructured":"Amura C\n                      , Brodsky KS, Groff R, Gattone VH, Voelkel NF, Doctor RB.\n                      VEGF receptor inhibition blocks liver cyst growth in pkd2(WS25\/\u2212) mice.\n                      Am J Physiol Cell Physiol\n                      293\n                      : C419\u2013C428, 2007.","DOI":"10.1152\/ajpcell.00038.2007"},{"key":"R5","doi-asserted-by":"crossref","unstructured":"Amura CR\n                      , Marek L, Winn RA, Heasley LE.\n                      Inhibited neurogenesis in JNK1-deficient embryonic stem cells.\n       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hormone-related protein by human breast cancer cells correlates with bone metastasis in vivo.\n                      Cancer Res\n                      62\n                      : 5571\u20135579, 2002."},{"key":"R8","doi-asserted-by":"crossref","unstructured":"Bijuklic K\n                      , Sturn DH, Jennings P, Kountchev J, Pfaller W, Wiedermann CJ, Patsch JR, Joannidis M.\n                      Mechanisms of neutrophil transmigration across renal proximal tubular HK-2 cells.\n                      Cell Physiol Biochem\n                      17\n                      : 233\u2013244, 2006.","DOI":"10.1159\/000094128"},{"key":"R9","doi-asserted-by":"crossref","unstructured":"Chapman AB\n                      , Guay-Woodford LM, Grantham JJ, Torres VE, Bae KT, Baumgarten DA, Kenney PJ, King BF Jr, Glockner JF, Wetzel LH, Brummer ME, O'Neill WC, Robbin ML, Bennett WM, Klahr S, Hirschman GH, Kimmel PL, Thompson PA, Miller JP.\n                      Renal structure in early autosomal-dominant polycystic kidney disease (ADPKD): The Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) cohort.\n                      Kidney Int\n                      64\n                      : 1035\u20131045, 2003.","DOI":"10.1046\/j.1523-1755.2003.00185.x"},{"key":"R10","doi-asserted-by":"crossref","unstructured":"Doctor RB\n                      , Dahl RH, Salter KD, Fitz JG.\n                      Reorganization of cholangiocyte membrane domains represents an early event in rat liver ischemia.\n                      Hepatology\n                      29\n                      : 1364\u20131374, 1999.","DOI":"10.1002\/hep.510290514"},{"key":"R11","doi-asserted-by":"crossref","unstructured":"Doctor RB\n                      , Johnson S, Brodsky KS, Amura CR, Gattone V, Fitz JG.\n                      Regulated ion transport in mouse liver cyst epithelial cells.\n                      Biochim Biophys Acta\n                      1772\n                      : 345\u2013354, 2007.","DOI":"10.1016\/j.bbadis.2006.11.006"},{"key":"R12","doi-asserted-by":"crossref","unstructured":"Everson G\n                      , Emmett M, Brown W, Redmond P, Thickman D.\n                      Functional similarities of hepatic and biliary epithelium: studies of fluid constituents and in vivo secretion in response to secretin.\n                      Hepatology\n                      11\n                      : 557\u2013565, 1990.","DOI":"10.1002\/hep.1840110406"},{"key":"R13","doi-asserted-by":"crossref","unstructured":"Fain PR\n                      , McFann KK, Taylor MRG, Tison M, Johnson AM, Reed B, Schrier RW.\n                      Modifier genes play a significant role in the phenotypic expression of PKD1.\n                      Kidney Int\n                      67\n                      : 1256\u20131267, 2005.","DOI":"10.1111\/j.1523-1755.2005.00203.x"},{"key":"R14","doi-asserted-by":"crossref","unstructured":"Freund A\n                      , Jolivel V, Durand S, Kersual N, Chalbos D, Chavey C, Vignon F, Lazennec G.\n                      Mechanisms underlying differential expression of interleukin-8 in breast cancer cells.\n                      Oncogene\n                      23\n                      : 6105\u20136114, 2004.","DOI":"10.1038\/sj.onc.1207815"},{"key":"R15","doi-asserted-by":"crossref","unstructured":"Galindo M\n                      , Santiago B, Alcami J, Rivero M, Martin-Serrano J, Pablos J.\n                      Hypoxia induces expression of the chemokines MCP-1 and IL-8 in human dermal fibroblasts.\n                      Clin Exp Immunol\n                      123\n                      : 36\u201341, 2001.","DOI":"10.1046\/j.1365-2249.2001.01412.x"},{"key":"R16","doi-asserted-by":"crossref","unstructured":"Gardner KJ\n                      , Burnside J, Elzinga L, Locksley R.\n                      Cytokines in fluids from polycystic kidneys.\n                      Kidney Int\n                      39\n                      : 718\u2013724, 1991.","DOI":"10.1038\/ki.1991.87"},{"key":"R17","doi-asserted-by":"crossref","unstructured":"Grantham JJ\n                      , Torres VE, Chapman AB, Guay-Woodford LM, Bae KT, King BF Jr, Wetzel LH, Baumgarten DA, Kenney PJ, Harris PC, Klahr S, Bennett WM, Hirschman GN, Meyers CM, Zhang X, Zhu F, Miller JP.\n                      Volume progression in polycystic kidney disease.\n                      N Engl J Med\n                      354\n                      : 2122\u20132130, 2006.","DOI":"10.1056\/NEJMoa054341"},{"key":"R18","doi-asserted-by":"crossref","unstructured":"Hateboer N\n                      , Veldhuisen B, Peters D, Breunning MH, San Millan JL, Bogdanova M, Coto E, van Dijk MA, Afzal AR, Jeffery S, Saggar-Malik AK, Torra R, Dimitrakov D, Martinez I, Sanz de Castro S, Krawczak K, Ravine D.\n                      Location of mutations within the PKD2 gene influences clinical outcomes.\n                      Kidney Int\n                      57\n                      : 1444\u20131451, 2000.","DOI":"10.1046\/j.1523-1755.2000.00989.x"},{"key":"R19","doi-asserted-by":"crossref","unstructured":"Hirani N\n                      , Antonicelli F, Strieter RM, Wiesener MS, Ratcliffe PJ, Haslett C, Donnelly SC.\n                      The regulation of interleukin-8 by hypoxia in human macrophages\u2013a potential role in the pathogenesis of the acute respiratory distress syndrome (ARDS).\n                      Mol Med\n                      7\n                      : 685\u2013697, 2001.","DOI":"10.1007\/BF03401959"},{"key":"R20","doi-asserted-by":"crossref","unstructured":"Holtmann H\n                      , Winzen R, Holland P, Eickemeier S, Hoffmann E, Wallach D, Malinin NL, Cooper JA, Resch K, Kracht M.\n                      Induction of interleukin-8 synthesis integrates effects on transcription and mRNA degradation from at least three different cytokine- or stress-activated signal transduction pathways.\n        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         , Sasaki T, Morinaka K, Kitadai Y, Mukaida N, Chayama K.\n                      Potential involvement of IL-8 and its receptors in the invasiveness of pancreatic cancer cells.\n                      Int J Oncol\n                      22\n                      : 765\u2013771, 2003.","DOI":"10.3892\/ijo.22.4.765"},{"key":"R24","doi-asserted-by":"crossref","unstructured":"Lee J\n                      , Horuk R, Rice G, Bennett G, Camerato T, Wood W.\n                      Characterization of two high affinity human IL-8 receptors.\n                      J Biol Chem\n                      267\n                      : 16283\u201316287, 1992.","DOI":"10.1016\/S0021-9258(18)41997-7"},{"key":"R25","doi-asserted-by":"crossref","unstructured":"Li A\n                      , Varney ML, Valasek J, Godfrey M, Dave BJ, Singh RK.\n                      Autocrine role of interleukin-8 in induction of endothelial cell proliferation, survival, migration and MMP-2 production and angiogenesis.\n   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     271\n                      : 14344\u201314352, 1996.","DOI":"10.1074\/jbc.271.24.14344"},{"key":"R28","doi-asserted-by":"crossref","unstructured":"Mitsuyama K\n                      , Toyonaga A, Sasaki E, Watanabe K, Tateishi H, Nishiyama T, Saiki T, Ikeda H, Tsuruta O, Tanikawa K.\n                      IL-8 as an important chemoattractant for neutrophils in ulcerative colitis and Crohn's disease.\n                      Clin Exp Immunol\n                      96\n                      : 432\u2013436, 1994.","DOI":"10.1111\/j.1365-2249.1994.tb06047.x"},{"key":"R29","doi-asserted-by":"crossref","unstructured":"Munemura C\n                      , Uemasu J, Kawasaki H.\n                      Epidermal growth factor and endothelin in cyst fluid from autosomal dominant polycystic kidney disease cases: possible evidence of heterogeneity in cystogenesis.\n                      Am J Kidney Dis\n                      24\n                      : 561\u2013568, 1994.","DOI":"10.1016\/S0272-6386(12)80212-5"},{"key":"R30","doi-asserted-by":"crossref","unstructured":"Nichols MT\n                      , Gidey E, Matzakos T, Dahl R, Stiegmann G, Shah RJ, Grantham JJ, Fitz JG, Doctor RB.\n                      Secretion of cytokines and growth factors into autosomal dominant polycystic kidney disease liver cyst fluid.\n                      Hepatology\n                      40\n                      : 836\u2013846, 2004.","DOI":"10.1002\/hep.20401"},{"key":"R31","doi-asserted-by":"crossref","unstructured":"Persu A\n                      , Duyme M, Pirson Y, Lens XM, Messiaen T, Breuning MH, Chauveau D, Levy M, Grunfeld JP, Devuyst O.\n                      Comparison between siblings and twins supports a role for modifier genes in ADPKD.\n                      Kidney Int\n                      66\n                      : 2132\u20132136, 2004.","DOI":"10.1111\/j.1523-1755.2004.66003.x"},{"key":"R32","doi-asserted-by":"crossref","unstructured":"Petreaca ML\n                      , Yao M, Liu Y, Defea K, Martins-Green M.\n                      Transactivation of vascular endothelial growth factor receptor-2 by interleukin-8 (IL-8\/CXCL8) Is required for IL-8\/CXCL8-induced endothelial permeability.\n                      Mol Biol Cell\n                      18\n                      : 5014\u20135023, 2007.","DOI":"10.1091\/mbc.e07-01-0004"},{"key":"R33","doi-asserted-by":"crossref","unstructured":"Remick DG\n                      .\n                      Interleukin-8.\n                      Crit Care Med\n                      33\n                      : S466\u2013S467, 2005.","DOI":"10.1097\/01.CCM.0000186783.34908.18"},{"key":"R34","doi-asserted-by":"crossref","unstructured":"Rossetti S\n                      , Burton S, Strmecki L, Pond GR, San Millan JL, Zerres K, Barratt TM, Ozen S, Torres VE, Bergstralh EJ, Winearls CG, Harris PC.\n                      The position of the polycystic kidney disease 1 (PKD1) gene mutation correlates with the severity of renal disease.\n                      J Am Soc Nephrol\n                      13\n                      : 1230\u20131237, 2002.","DOI":"10.1097\/01.ASN.0000013300.11876.37"},{"key":"R35","doi-asserted-by":"crossref","unstructured":"Savage SA\n                      , Abnet CC, Mark SD, Qiao YL, Dong ZW, Dawsey SM, Taylor PR, Chanock SJ.\n                      Variants of the IL8 and IL8RB genes and risk for gastric cardia adenocarcinoma and esophageal squamous cell carcinoma.\n                      Cancer Epidemiol Biomarkers Prev\n                      13\n                      : 2251\u20132257, 2004.","DOI":"10.1158\/1055-9965.2251.13.12"},{"key":"R36","doi-asserted-by":"crossref","unstructured":"Shi Q\n                      , Xiong Q, Le X, Xie K.\n                      Regulation of interleukin-8 expression by tumor-associated stress 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1995.","DOI":"10.1681\/ASN.V641230"},{"key":"R39","doi-asserted-by":"crossref","unstructured":"Torres VE\n                      , Harris PC, Pirson Y.\n                      Autosomal dominant polycystic kidney disease.\n                      Lancet\n                      369\n                      : 1287\u20131301, 2007.","DOI":"10.1016\/S0140-6736(07)60601-1"},{"key":"R40","doi-asserted-by":"crossref","unstructured":"Torres VE\n                      , Sweeney WE, Wang X, Qian Q, Harris PC, Frost P, Avner ED.\n                      EGF receptor tyrosine kinase inhibition attenuates the development of PKD in Han:SPRD rats.\n                      Kidney Int\n                      64\n                      : 1573\u20131579, 2003.","DOI":"10.1046\/j.1523-1755.2003.00256.x"},{"key":"R41","doi-asserted-by":"crossref","unstructured":"Vlahakis N\n                      , Schroeder M, Limper A, Hubmayr R.\n                      Stretch induces cytokine release by alveolar epithelial cells in 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Liver transplantation for polycystic liver disease.\n                      N Engl J Med\n                      356\n                      : 1560, 2007.","DOI":"10.1056\/NEJMicm055470"},{"key":"R43","doi-asserted-by":"crossref","unstructured":"Wang B\n                      , Hendricks DT, Wamunyokoli F, Parker MI.\n                      A growth-related oncogene\/CXC chemokine receptor 2 autocrine loop contributes to cellular proliferation in esophageal cancer.\n                      Cancer Res\n                      66\n                      : 3071\u20133077, 2006.","DOI":"10.1158\/0008-5472.CAN-05-2871"},{"key":"R44","unstructured":"Wang Y\n                      , Yang J, Gao Y, Du Y, Bao L, Niu W, Yao Z.\n                      Regulatory effect of e2, IL-6 and IL-8 on the growth of epithelial ovarian cancer cells.\n                      Cell Mol Immunol\n                      2\n                      : 365\u2013372, 2005."},{"key":"R45","doi-asserted-by":"crossref","unstructured":"Wu G\n                      , D'Agati V, Cai Y, Markowitz GS, Park JH, Reynolds DM, Maeda Y, Le TC, Hou H Jr, Kucherlapati R, Edelmann W, Somlo S.\n                      Somatic inactivation of Pkd2 results in polycystic kidney disease.\n                      Cell\n                      93\n                      : 177\u2013188, 1998.","DOI":"10.1016\/S0092-8674(00)81570-6"}],"container-title":["American Journal of Physiology-Cell Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajpcell.00457.2007","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T13:27:36Z","timestamp":1718630856000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajpcell.00457.2007"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,3]]},"references-count":45,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2008,3]]}},"alternative-id":["10.1152\/ajpcell.00457.2007"],"URL":"https:\/\/doi.org\/10.1152\/ajpcell.00457.2007","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1103536.559603","asserted-by":"object"}]},"ISSN":["0363-6143","1522-1563"],"issn-type":[{"value":"0363-6143","type":"print"},{"value":"1522-1563","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,3]]}}}