{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:53:29Z","timestamp":1786978409076,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2013,7,1]],"date-time":"2013-07-01T00:00:00Z","timestamp":1372636800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Prostate UK, Prostate Action"},{"name":"Wellcome Trust Clinical Training Fellowship"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2013,10]]},"abstract":"Abstract<\/jats:title>\n \n BACKGROUND<\/jats:title>\n This study investigated whether the increase in serum prostate specific antigen (PSA) typically seen during male urinary tract infection (UTI) is incidental or reflects an innate defence mechanism of the prostate. The protective roles of the whey\u2010acid\u2010motif\u20104\u2010disulphide core (WFDC) proteins, secretory leukoproteinase inhibitor (SLPI) and WFDC2, in the prostate were also examined.<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n \n UTI recurrence was assessed retrospectively in men following initial UTI by patient interview. PSA, SLPI, and WFDC2 gene expression were assessed using biopsy samples. LNCaP and DU145 in vitro prostate cell models were utilized to assess the effects of an\n Escherichia coli<\/jats:italic>\n challenge on PSA and WFDC gene expression, and bacterial invasion of the prostate epithelium. The effects of PSA on WFDC antimicrobial properties were studied using recombinant peptides and time\u2010kill assays.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n Men presenting with PSA\u2009>4\u2009ng\/ml at initial UTI were less likely to have recurrent (r) UTI than those with PSA\u2009<4\u2009ng\/ml [2\/15 (13%) vs. 7\/10 (70%),\n P<\/jats:italic>\n \u2009<\u20090.01]. Genes encoding PSA, SLPI and WFDC2, were expressed in prostatic epithelium, and the PSA and SLPI proteins co\u2010localized in vivo. Challenging LNCaP (PSA\u2010positive) cells with\n E. coli<\/jats:italic>\n increased\n PSA, SLPI<\/jats:italic>\n , and\n WFDC2<\/jats:italic>\n gene expression (\n P<\/jats:italic>\n \u2009<\u20090.05), and PSA synthesis (\n P<\/jats:italic>\n \u2009<\u20090.05), and reduced bacterial invasion. Pre\u2010incubation of DU145 (PSA\u2010negative) cells with PSA also decreased bacterial invasion. In vitro incubation of recombinant SLPI and WFDC2 with PSA resulted in peptide proteolysis and increased\n E. coli<\/jats:italic>\n killing.\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS<\/jats:title>\n \n Increased PSA during UTI appears protective against rUTI and in vitro is linked to proteolysis of WFDC proteins supporting enhanced prostate innate defences.\n Prostate 73: 1529\u20131537, 2013<\/jats:italic>\n . \u00a9 2013 Wiley Periodicals, Inc.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/pros.22700","type":"journal-article","created":{"date-parts":[[2013,7,1]],"date-time":"2013-07-01T13:16:18Z","timestamp":1372684578000},"page":"1529-1537","source":"Crossref","is-referenced-by-count":10,"title":["Prostate specific antigen enhances the innate defence of prostatic epithelium against\n Escherichia coli<\/i>\n infection"],"prefix":"10.1002","volume":"73","author":[{"given":"Claire L","family":"Townes","sequence":"first","affiliation":[{"name":"Institute for Cell and Molecular Biosciences Newcastle University Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ased","family":"Ali","sequence":"additional","affiliation":[{"name":"Institute of Cellular Medicine Newcastle University Newcastle upon Tyne UK"},{"name":"Department of Urology Newcastle upon Tyne Hospitals NHS Foundation Trust Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Gross","sequence":"additional","affiliation":[{"name":"Institute of Cellular Medicine Newcastle University Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepali","family":"Pal","sequence":"additional","affiliation":[{"name":"Northern Institute for Cancer Research Newcastle University Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart","family":"Williamson","sequence":"additional","affiliation":[{"name":"Northern Institute for Cancer Research Newcastle University Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakesh","family":"Heer","sequence":"additional","affiliation":[{"name":"Northern Institute for Cancer Research Newcastle University Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig N","family":"Robson","sequence":"additional","affiliation":[{"name":"Northern Institute for Cancer Research Newcastle University Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert S","family":"Pickard","sequence":"additional","affiliation":[{"name":"Institute of Cellular Medicine Newcastle University Newcastle upon Tyne UK"},{"name":"Department of Urology Newcastle upon Tyne Hospitals NHS Foundation Trust Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Hall","sequence":"additional","affiliation":[{"name":"Institute for Cell and Molecular Biosciences Newcastle University Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,7]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2007.07.044"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.282.3.236"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/00042307-200301000-00005"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464-410x.1999.00164.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112185"},{"issue":"15","key":"e_1_2_7_7_1","first-page":"3111","article-title":"Expression of pro form of prostate\u2010specific antigen by mammalian cells and its conversion to mature, active form by human kallikrein 2","volume":"57","author":"Kumar A","year":"1997","journal-title":"Cancer Res"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.3109\/00365518409083836"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1939-4640.1989.tb00134.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.5.3413"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.104.036483"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2006-7-5-r40"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2008.07.001"},{"issue":"2","key":"e_1_2_7_14_1","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1042\/BST0340267","article-title":"Characterization of AWAP IV, the C\u2010terminal domain of the avian protein AWAK","volume":"34","author":"Townes CL","year":"2006","journal-title":"Biochem Soc Trans"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20050115"},{"issue":"5","key":"e_1_2_7_16_1","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1042\/BST0391409","article-title":"WAP domain proteins as modulators of mucosal immunity","volume":"39","author":"Wilkinson TS","journal-title":"Biochem Soc Trans"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1308\/10.1308\/147870811X589245"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21154"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.12.6987-6993.2004"},{"key":"e_1_2_7_20_1","first-page":"67","article-title":"Characterization of a human prostate adenocarcinoma cell line (DU 145) as a monolayer culture and as a solid tumor in athymic mice","volume":"37","author":"Mickey DD","year":"1980","journal-title":"Prog Clin Biol Res"},{"key":"e_1_2_7_21_1","first-page":"115","article-title":"The LNCaP cell line\u2014A new model for studies on human prostatic carcinoma","volume":"37","author":"Horoszewicz JS","year":"1980","journal-title":"Prog Clin Biol Res"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1939-4640.1995.tb01733.x"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.64.11.4520-4524.1996"},{"issue":"1","key":"e_1_2_7_24_1","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/j.1365-2559.2011.04033.x","article-title":"Prostate cancer and inflammation: The evidence","volume":"60","author":"Sfanos KS","journal-title":"Histopathology"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.20414"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.2990200206"},{"issue":"1","key":"e_1_2_7_27_1","first-page":"185","article-title":"On a hormone dependent inhibitor of proteolytic enzymes in male accessory sex glands and in sperm","volume":"343","author":"Haendle H","year":"1965","journal-title":"Hoppe Seylers Z Physiol Chem"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65517-4"},{"issue":"4","key":"e_1_2_7_29_1","first-page":"L601","article-title":"Corticosteroids increase secretory leukocyte protease inhibitor transcript levels in airway epithelial cells","volume":"268","author":"Abbinante\u2010Nissen JM","year":"1995","journal-title":"Am J Physiol"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1590\/S1677-55382009000300006"},{"issue":"3","key":"e_1_2_7_31_1","first-page":"287","article-title":"Zinc levels in prostatic fluid of patients with prostate pathologies","volume":"48","author":"Gomez Y","year":"2007","journal-title":"Invest Clin"},{"issue":"6","key":"e_1_2_7_32_1","first-page":"530","article-title":"Changes of seminal parameters, zinc concentration and antibacterial activity in patients with non\u2010inflammatory chronic prostatitis\/chronic pelvic pain syndrome","volume":"14","author":"Zhao H","year":"2008","journal-title":"Zhonghua Nan Ke Xue"},{"issue":"5","key":"e_1_2_7_33_1","first-page":"368","article-title":"Clinical study of zinc for the treatment of chronic bacterial prostatitis","volume":"10","author":"Deng C","year":"2004","journal-title":"Zhonghua Nan Ke Xue"}],"container-title":["The Prostate"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpros.22700","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpros.22700","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pros.22700","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T06:44:40Z","timestamp":1696488280000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pros.22700"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,7]]},"references-count":32,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2013,10]]}},"alternative-id":["10.1002\/pros.22700"],"URL":"https:\/\/doi.org\/10.1002\/pros.22700","archive":["Portico"],"relation":{},"ISSN":["0270-4137","1097-0045"],"issn-type":[{"value":"0270-4137","type":"print"},{"value":"1097-0045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,7]]}}}