{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T09:44:40Z","timestamp":1772012680135,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,12,17]],"date-time":"2013-12-17T00:00:00Z","timestamp":1387238400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["P20-DK090919"],"award-info":[{"award-number":["P20-DK090919"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Prostatic inflammation is associated with the development of prostatic hyperplasia. We investigated the effects of prostatic inflammation on expression levels of androgen\u2010responsive genes and growth factors in the prostate.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Prostatic inflammation was induced by formalin injection into bilateral ventral lobes of the prostate of male SD rats. After 28 days, the prostate was harvested for analyses of proinflammatory cytokines, androgen\u2010responsive genes in the epithelium, and TGF\u2010\u03b21 cascade genes in the stroma. Some rats were given a COX\u20102 inhibitor (celecoxib; 10\u2009mg\/kg\/day) by oral gavage for 28 days.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>The formalin\u2010injected prostate exhibited widespread low\u2010grade inflammation (&lt;50\u2009leukocytes\/10,000\u2009\u03bcm<jats:sup>2<\/jats:sup>) along with focal high\u2010grade inflammation (&gt;100\u2009leukocytes\/10,000\u2009\u03bcm<jats:sup>2<\/jats:sup>) in limited areas. Compared to control, formalin\u2010injected prostate exhibited a 2.5\u2010fold to sixfold increased protein expression of IL\u20101\u03b1, IL\u20101\u03b2, and IL\u20106. In the low\u2010grade inflammatory regions, threefold to ninefold and twofold to threefold upregulations of mRNA levels of androgen receptors\/androgen\u2010responsive genes and TGF\u2010\u03b21 cascade genes were respectively, observed in the epithelium and stroma obtained by laser\u2010capture microdissection. Positive staining for androgen receptors in the epithelial nuclei, and TGF\u2010\u03b21, IL\u20106, and COX\u20102 in the stroma was increased in the low\u2010grade inflammation area. COX\u20102 inhibitor treatment suppressed these upregulations of cytokines, androgen\u2010responsive, and TGF\u2010\u03b21 cascade genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Prostatic inflammation induced increased expression of androgen\u2010responsive genes in the epithelium and TGF\u2010\u03b21 cascade genes in the stroma, which were suppressed by COX\u20102 inhibitors, suggesting that activation of these genes in the low\u2010grade inflammatory region might be involved in the development of symptomatic BPH. <jats:italic>Prostate 74:337\u2013345, 2014<\/jats:italic>. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.22668","type":"journal-article","created":{"date-parts":[[2013,12,17]],"date-time":"2013-12-17T14:30:51Z","timestamp":1387290651000},"page":"337-345","source":"Crossref","is-referenced-by-count":36,"title":["Upregulation of androgen\u2010responsive genes and transforming growth factor\u2010\u03b21 cascade genes in a rat model of non\u2010bacterial prostatic inflammation"],"prefix":"10.1002","volume":"74","author":[{"given":"Yasuhito","family":"Funahashi","sequence":"first","affiliation":[{"name":"Departments of Urology University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania"},{"name":"Department of Urology Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine J.","family":"O'Malley","sequence":"additional","affiliation":[{"name":"Departments of Urology University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoki","family":"Kawamorita","sequence":"additional","affiliation":[{"name":"Departments of Urology University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pradeep","family":"Tyagi","sequence":"additional","affiliation":[{"name":"Departments of Urology University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald B.","family":"DeFranco","sequence":"additional","affiliation":[{"name":"Departments of Pharmacology &amp; Chemical Biology University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryosuke","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Departments of Urology University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Momokazu","family":"Gotoh","sequence":"additional","affiliation":[{"name":"Department of Urology Nagoya University Graduate School of Medicine Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhou","family":"Wang","sequence":"additional","affiliation":[{"name":"Departments of Urology University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoki","family":"Yoshimura","sequence":"additional","affiliation":[{"name":"Departments of Urology University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania"},{"name":"Departments of Pharmacology &amp; Chemical Biology University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,12,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2007.11.026"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2007.06910.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)65140-3"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2006.06098.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-12-0142"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2009.02.064"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diff.2011.06.001"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.21081"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0801875"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.21034"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.84.10.3463"},{"key":"e_1_2_7_13_1","first-page":"5","article-title":"Prostatic growth: New insights into hormonal regulation","volume":"76","author":"McConnell JD","year":"1995","journal-title":"Br J Urol"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/08977190412331279908"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.20553"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.20691"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.21027"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0812666106"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2011-1371"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.21124"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.20061"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(96)90396-2"},{"issue":"19","key":"e_1_2_7_23_1","first-page":"4245","article-title":"NS398, a selective cyclooxygenase\u20102 inhibitor, induces apoptosis and down\u2010regulates bcl\u20102 expression in LNCaP cells","volume":"58","author":"Liu XH","year":"1998","journal-title":"Cancer Res"},{"issue":"3","key":"e_1_2_7_24_1","first-page":"820","article-title":"Inhibition of cyclooxygenase\u20102 suppresses angiogenesis and the growth of prostate cancer in vivo","volume":"164","author":"Liu XH","year":"2000","journal-title":"J Urol"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.21150"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1939-4640.2004.tb02758.x"},{"issue":"9","key":"e_1_2_7_27_1","first-page":"2912","article-title":"Reactive stroma in human prostate cancer: Induction of myofibroblast phenotype and extracellular matrix remodeling","volume":"8","author":"Tuxhorn JA","year":"2002","journal-title":"Clin Cancer Res"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.21327"},{"issue":"3","key":"e_1_2_7_29_1","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/S0094-0143(21)00960-5","article-title":"Clinical and experimental studies of benign prostatic hyperplasia","volume":"17","author":"Coffey DS","year":"1990","journal-title":"Urol Clin North Am"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210786"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.080417"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2006.11.010"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2011.08.010"},{"issue":"8","key":"e_1_2_7_34_1","first-page":"769","article-title":"The cyclooxygenase 2\u2010specific nonsteroidal anti\u2010inflammatory drugs celecoxib and nimesulide inhibit androgen receptor activity via induction of c\u2010Jun in prostate cancer cells","volume":"12","author":"Pan Y","year":"2003","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1207\/s15327914nc5202_10"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwj258"}],"container-title":["The Prostate"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpros.22668","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpros.22668","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pros.22668","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T07:22:32Z","timestamp":1696490552000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pros.22668"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,12,17]]},"references-count":35,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2014,4]]}},"alternative-id":["10.1002\/pros.22668"],"URL":"https:\/\/doi.org\/10.1002\/pros.22668","archive":["Portico"],"relation":{},"ISSN":["0270-4137","1097-0045"],"issn-type":[{"value":"0270-4137","type":"print"},{"value":"1097-0045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,12,17]]}}}