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Published in: Inflammation Research 1/2018

01-01-2018 | Original Research Paper

Intraurethral injection with LPS: an effective experimental model of prostatic inflammation

Authors: Fabiana Oliveira dos Santos Gomes, Amanda Costa Oliveira, Edlene Lima Ribeiro, Bruna Santos da Silva, Laise Aline Martins dos Santos, Ingrid Tavares de Lima, Amanda Karolina Soares e Silva, Shyrlene Meiry da Rocha Araújo, Terezinha Gonçalves, Mario Ribeiro de Melo-Junior, Christina Alves Peixoto

Published in: Inflammation Research | Issue 1/2018

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Abstract

Objective

Chronic inflammation has been recognized as having a prominent role pathogenesis of benign prostatic hyperplasia (BPH) and cancer. It is believed that chronic inflammation induces prostatic fibromuscular growth. This correlation has been clearly illustrated by both in vivo and in vitro studies; however, current experimental models of BPH require complex surgery or hormonal treatment. Therefore, the aim of the present study was to propose a new murine model of BPH/prostatitis induced by intraurethral injection of LPS.

Methods

Male Swiss and C57Bl/6 mice were then sacrificed 3, 7, 10, and 14 days after intraurethral injection of LPS. The prostates were quickly dissected and fixed for morphological and immunohistochemical analyses.

Results

The results showed that LPS played an important role in the cell proliferation of the prostate. Histological and ultrastructural analysis showed epithelial hyperplasia, clear stromal cells, little inflammatory infiltration, and heavy bleeding. Treatment with LPS also promoted the increase of growth factor (FGF-7 and TGF-β), α-actin, and proinflammatory cytokines (IL-1, IL-6, IL-17), both in the stroma and epithelium.

Conclusion

According to the present findings, it can be concluded that the intraurethral administration of LPS promotes tissue remodeling, as well as stimulating the pattern of pro-inflammatory cytokines, and therefore, constitutes an effective experimental model of BPH/inflammation.
Literature
1.
go back to reference Hamid AR, Umbas R, Mochtar CA. Recent role of inflammation in prostate diseases: chemoprevention development opportunity. Acta Med Indones. 2011;43:59–65.PubMed Hamid AR, Umbas R, Mochtar CA. Recent role of inflammation in prostate diseases: chemoprevention development opportunity. Acta Med Indones. 2011;43:59–65.PubMed
2.
go back to reference Omabe M, Ezeani M. Infection, inflammation and prostate carcinogenesis. Infect Genet Evol. 2011;11:1195–8.CrossRefPubMed Omabe M, Ezeani M. Infection, inflammation and prostate carcinogenesis. Infect Genet Evol. 2011;11:1195–8.CrossRefPubMed
4.
go back to reference Wang X, Zhong S, Xu T, Xia L, Zhang X, Zhu Z, Zhang M, Shen Z. Histopathological classification criteria of rat model of chronic prostatitis/chronic pelvic pain syndrome. Int Urol Nephrol. 2015;47:307–16.CrossRefPubMed Wang X, Zhong S, Xu T, Xia L, Zhang X, Zhu Z, Zhang M, Shen Z. Histopathological classification criteria of rat model of chronic prostatitis/chronic pelvic pain syndrome. Int Urol Nephrol. 2015;47:307–16.CrossRefPubMed
5.
go back to reference De Marzo AM, Nakai Y, Nelson WG. Inflammation, atrophy, and prostate carcinogenesis. Urol Oncol. 2007;25:398–400.CrossRefPubMed De Marzo AM, Nakai Y, Nelson WG. Inflammation, atrophy, and prostate carcinogenesis. Urol Oncol. 2007;25:398–400.CrossRefPubMed
6.
go back to reference De Nunzio C, Kramer G, Marberger M, Montironi R, Nelson W, Schröder F, Sciarra A, Tubaro A. The controversial relationship between benign prostatic hyperplasia and prostate cancer: the role of inflammation. Eur Urol. 2011;60:106–17.CrossRefPubMed De Nunzio C, Kramer G, Marberger M, Montironi R, Nelson W, Schröder F, Sciarra A, Tubaro A. The controversial relationship between benign prostatic hyperplasia and prostate cancer: the role of inflammation. Eur Urol. 2011;60:106–17.CrossRefPubMed
7.
go back to reference Robert G, Smit F, Hessels D, Jannink S, Karthaus HF, Aalders T, Jansen K, de la Taille A, Mulders PF, Schalken JA. Biomarkers for the diagnosis of prostatic inflammation in benign prostatic hyperplasia. Prostate. 2011;71:1701–9.CrossRefPubMed Robert G, Smit F, Hessels D, Jannink S, Karthaus HF, Aalders T, Jansen K, de la Taille A, Mulders PF, Schalken JA. Biomarkers for the diagnosis of prostatic inflammation in benign prostatic hyperplasia. Prostate. 2011;71:1701–9.CrossRefPubMed
8.
go back to reference Elkahwaji JE. The role of inflammatory mediators in the development of prostatic hyperplasia and prostate cancer. Res Rep Urol. 2012;31:1–10. Elkahwaji JE. The role of inflammatory mediators in the development of prostatic hyperplasia and prostate cancer. Res Rep Urol. 2012;31:1–10.
9.
go back to reference Thapa D, Ghosh R. Chronic inflammatory mediators enhance prostate cancer development and progression. Biochem Pharmacol. 2015;94:53–62.CrossRefPubMed Thapa D, Ghosh R. Chronic inflammatory mediators enhance prostate cancer development and progression. Biochem Pharmacol. 2015;94:53–62.CrossRefPubMed
10.
go back to reference Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;24:436–44.CrossRef Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;24:436–44.CrossRef
11.
go back to reference De Marzo AM, Platz EA, Sutcliffe S, Xu J, Grönberg H, Drake CG, Nakai Y, Isaacs WB, Nelson WG. Inflammation in prostate carcinogenesis. Nat Rev Cancer. 2007;7:256–69.CrossRefPubMedPubMedCentral De Marzo AM, Platz EA, Sutcliffe S, Xu J, Grönberg H, Drake CG, Nakai Y, Isaacs WB, Nelson WG. Inflammation in prostate carcinogenesis. Nat Rev Cancer. 2007;7:256–69.CrossRefPubMedPubMedCentral
12.
go back to reference Vykhovanets EV, Resnick MI, MacLennan GT, Gupta S. Experimental rodent models of prostatitis: limitations and potential. Prostate Cancer Prostat Dis. 2007;10:15–29.CrossRef Vykhovanets EV, Resnick MI, MacLennan GT, Gupta S. Experimental rodent models of prostatitis: limitations and potential. Prostate Cancer Prostat Dis. 2007;10:15–29.CrossRef
13.
go back to reference Li TF, Li WW, Xia XY, Huang YF. Animal models of chronic prostatitis: an update. Zhonghua Nan Ke Xue. 2013;19:1124–8.PubMed Li TF, Li WW, Xia XY, Huang YF. Animal models of chronic prostatitis: an update. Zhonghua Nan Ke Xue. 2013;19:1124–8.PubMed
14.
go back to reference Fulmer BR, Turner TT. Effect of inflammation on prostatic protein synthesis and luminal secretion in vivo. J Urol. 1999;162:248–53.CrossRefPubMed Fulmer BR, Turner TT. Effect of inflammation on prostatic protein synthesis and luminal secretion in vivo. J Urol. 1999;162:248–53.CrossRefPubMed
15.
go back to reference Mosli HA, Al-Abd AM, El-Shaer MA, Khedr A, Gazzaz FS, Abdel-Naim AB. Local inflammation influences oestrogen metabolism in prostatic tissue. BJU Int. 2012;110:274–82.CrossRefPubMed Mosli HA, Al-Abd AM, El-Shaer MA, Khedr A, Gazzaz FS, Abdel-Naim AB. Local inflammation influences oestrogen metabolism in prostatic tissue. BJU Int. 2012;110:274–82.CrossRefPubMed
16.
go back to reference Elkahwaji JE, Zhong W, Hopkins WJ, Bushman W. Chronic bacterial infection and inflammation incite reactive hyperplasia in a mouse model of chronic prostatitis. Prostate. 2007;67:14–21.CrossRefPubMed Elkahwaji JE, Zhong W, Hopkins WJ, Bushman W. Chronic bacterial infection and inflammation incite reactive hyperplasia in a mouse model of chronic prostatitis. Prostate. 2007;67:14–21.CrossRefPubMed
17.
go back to reference Elkahwaji JE, Hauke RJ, Brawner CM. Chronic bacterial inflammation induces prostatic intraepithelial neoplasia in mouse prostate. Br J Cancer. 2009;101:1740–8.CrossRefPubMedPubMedCentral Elkahwaji JE, Hauke RJ, Brawner CM. Chronic bacterial inflammation induces prostatic intraepithelial neoplasia in mouse prostate. Br J Cancer. 2009;101:1740–8.CrossRefPubMedPubMedCentral
18.
go back to reference Boehm BJ, Colopy SA, Jerde TJ, Loftus CJ, Bushman W. Acute bacterial inflammation of the mouse prostate. Prostate. 2012;72:307–17.CrossRefPubMed Boehm BJ, Colopy SA, Jerde TJ, Loftus CJ, Bushman W. Acute bacterial inflammation of the mouse prostate. Prostate. 2012;72:307–17.CrossRefPubMed
19.
go back to reference Elkahwaji JE, Ott CJ, Janda LM, Hopkins WJ. Mouse model for acute bacterial prostatitis in genetically distinct inbred strains. Urology. 2005;66:883–7.CrossRefPubMed Elkahwaji JE, Ott CJ, Janda LM, Hopkins WJ. Mouse model for acute bacterial prostatitis in genetically distinct inbred strains. Urology. 2005;66:883–7.CrossRefPubMed
20.
go back to reference Roehrborn CG. Alfuzosin 10 mg once daily prevents overall clinical progression of benign prostatic hyperplasia but not acute urinary retention: results of a 2-year placebo-controlled study. BJU Int. 2006;97(4):734–41.CrossRefPubMed Roehrborn CG. Alfuzosin 10 mg once daily prevents overall clinical progression of benign prostatic hyperplasia but not acute urinary retention: results of a 2-year placebo-controlled study. BJU Int. 2006;97(4):734–41.CrossRefPubMed
21.
go back to reference Nickel JC. Inflammation and benign prostatic hyperplasia. Urol Clin N Am. 2008;35(1):109–15.CrossRef Nickel JC. Inflammation and benign prostatic hyperplasia. Urol Clin N Am. 2008;35(1):109–15.CrossRef
22.
go back to reference Sciarra A, Di Silverio F, Salciccia S, Gomez AM, Gentilucci A, Gentile V. Inflammation and chronic prostatic diseases: evidence for a link? Eur Urol. 2007;52(4):964–72.CrossRefPubMed Sciarra A, Di Silverio F, Salciccia S, Gomez AM, Gentilucci A, Gentile V. Inflammation and chronic prostatic diseases: evidence for a link? Eur Urol. 2007;52(4):964–72.CrossRefPubMed
23.
go back to reference Peehl DM, Rubin JS. Keratinocyte growth factor: an androgen-regulated mediator of stromal-epithelial interactions in the prostate. World J Urol. 1995;13(5):312–7.PubMed Peehl DM, Rubin JS. Keratinocyte growth factor: an androgen-regulated mediator of stromal-epithelial interactions in the prostate. World J Urol. 1995;13(5):312–7.PubMed
24.
go back to reference Ma J, Gharaee-Kermani M, Kunju L, Hollingsworth JM, Adler J, Arruda EM, Macoska JA. Prostatic fibrosis is associated with lower urinary tract symptoms. J Urol. 2012;188(4):1375–81.CrossRefPubMedPubMedCentral Ma J, Gharaee-Kermani M, Kunju L, Hollingsworth JM, Adler J, Arruda EM, Macoska JA. Prostatic fibrosis is associated with lower urinary tract symptoms. J Urol. 2012;188(4):1375–81.CrossRefPubMedPubMedCentral
25.
go back to reference Cantiello F, Cicione A, Salonia A, Autorino R, Tucci L, Madeo I, Damiano R. Periurethral fibrosis secondary to prostatic inflammation causing lower urinary tract symptoms: a prospective cohort study. Urology. 2013;81(5):1018–23.CrossRefPubMed Cantiello F, Cicione A, Salonia A, Autorino R, Tucci L, Madeo I, Damiano R. Periurethral fibrosis secondary to prostatic inflammation causing lower urinary tract symptoms: a prospective cohort study. Urology. 2013;81(5):1018–23.CrossRefPubMed
26.
27.
go back to reference Wong L, Hutson PR, Bushman W. Resolution of chronic bacterial-induced prostatic inflammation reverses established fibrosis. Prostate. 2015;75(1):23–32.CrossRefPubMed Wong L, Hutson PR, Bushman W. Resolution of chronic bacterial-induced prostatic inflammation reverses established fibrosis. Prostate. 2015;75(1):23–32.CrossRefPubMed
28.
go back to reference Lohrer P, Gloddek J, Nagashima AC, Korali Z, Hopfner U, Pereda MP, Arzt E, Stalla GK, Renner U. Lipopolysaccharide directly stimulates the intrapituitary interleukin-6 production by folliculostellate cells via specific receptors and the p38 alpha mitogen-activated protein kinase/nuclear factor-kappaB pathway. Endocrinology. 2000;141(12):4457–65.CrossRefPubMed Lohrer P, Gloddek J, Nagashima AC, Korali Z, Hopfner U, Pereda MP, Arzt E, Stalla GK, Renner U. Lipopolysaccharide directly stimulates the intrapituitary interleukin-6 production by folliculostellate cells via specific receptors and the p38 alpha mitogen-activated protein kinase/nuclear factor-kappaB pathway. Endocrinology. 2000;141(12):4457–65.CrossRefPubMed
29.
go back to reference Ikezoe T, Yang Y, Heber D, Taguchi H, Koeffler HP. PC-SPES: a potent inhibitor of nuclear factor-kappa B rescues mice from lipopolysaccharide-induced septic shock. Mol Pharmacol. 2003;64(6):1521–9.CrossRefPubMed Ikezoe T, Yang Y, Heber D, Taguchi H, Koeffler HP. PC-SPES: a potent inhibitor of nuclear factor-kappa B rescues mice from lipopolysaccharide-induced septic shock. Mol Pharmacol. 2003;64(6):1521–9.CrossRefPubMed
30.
go back to reference Kwak HJ, Song JS, Heo JY, Yang SD, Nam JY, Cheon HG. Roflumilast inhibits lipopolysaccharide-induced inflammatory mediators via suppression of nuclear factor-kappaB, p38 mitogen-activated protein kinase, and c-Jun NH2-terminal kinase activation. J Pharmacol Exp Ther. 2005;315(3):1188–95.CrossRefPubMed Kwak HJ, Song JS, Heo JY, Yang SD, Nam JY, Cheon HG. Roflumilast inhibits lipopolysaccharide-induced inflammatory mediators via suppression of nuclear factor-kappaB, p38 mitogen-activated protein kinase, and c-Jun NH2-terminal kinase activation. J Pharmacol Exp Ther. 2005;315(3):1188–95.CrossRefPubMed
31.
go back to reference Iglesias-Gato D, Carsten T, Vesterlund M, Pousette A, Schoop R, Norstedt G. Androgen-independent effects of Serenoa repens extract (Prostasan®) on prostatic epithelial cell proliferation and inflammation. Phytother Res. 2012;26(2):259–64.CrossRefPubMed Iglesias-Gato D, Carsten T, Vesterlund M, Pousette A, Schoop R, Norstedt G. Androgen-independent effects of Serenoa repens extract (Prostasan®) on prostatic epithelial cell proliferation and inflammation. Phytother Res. 2012;26(2):259–64.CrossRefPubMed
32.
go back to reference Kramer G, Mitteregger D, Marberger M. Is benign prostatic hyperplasia (BPH) an immune inflammatory disease? Eur Urol. 2007;51:1202–16.CrossRefPubMed Kramer G, Mitteregger D, Marberger M. Is benign prostatic hyperplasia (BPH) an immune inflammatory disease? Eur Urol. 2007;51:1202–16.CrossRefPubMed
33.
go back to reference Steiner GE, Stix U, Handisurya A, Willheim M, Haitel A, Reithmayr F, et al. Cytokine expression pattern in benign prostatic hyperplasia infiltrating T cells and impact of lymphocytic infiltration on cytokine mRNA profile in prostatic tissue. Lab Invest. 2003;83:1131–46.CrossRefPubMed Steiner GE, Stix U, Handisurya A, Willheim M, Haitel A, Reithmayr F, et al. Cytokine expression pattern in benign prostatic hyperplasia infiltrating T cells and impact of lymphocytic infiltration on cytokine mRNA profile in prostatic tissue. Lab Invest. 2003;83:1131–46.CrossRefPubMed
34.
go back to reference Fibbi B, Morelli A, Vignozzi L, Filippi S, Chavalmane A, De Vita G, Marini M, Gacci M, Vannelli GB, Sandner P, Maggi M. Characterization of phosphodiesterase type 5 expression and functional activity in the human male lower urinary tract. J Sex Med. 2010;7:59–69.CrossRefPubMed Fibbi B, Morelli A, Vignozzi L, Filippi S, Chavalmane A, De Vita G, Marini M, Gacci M, Vannelli GB, Sandner P, Maggi M. Characterization of phosphodiesterase type 5 expression and functional activity in the human male lower urinary tract. J Sex Med. 2010;7:59–69.CrossRefPubMed
35.
go back to reference Jerde TJ, Bushman W. IL-1 induces IGF-dependent epithelial proliferation in prostate development and reactive hyperplasia. Sci Signal. 2009;86:ra49. Jerde TJ, Bushman W. IL-1 induces IGF-dependent epithelial proliferation in prostate development and reactive hyperplasia. Sci Signal. 2009;86:ra49.
36.
go back to reference Liu X, Piao YS, Arnold JT. Transforming growth factor β1 increase of hydroxysteroid dehydrogenase proteins is partly suppressed by red clover isoflavones in human primary prostate cancer-derived stromal cells. Carcinogenesis. 2011;32:1648–54.CrossRefPubMedPubMedCentral Liu X, Piao YS, Arnold JT. Transforming growth factor β1 increase of hydroxysteroid dehydrogenase proteins is partly suppressed by red clover isoflavones in human primary prostate cancer-derived stromal cells. Carcinogenesis. 2011;32:1648–54.CrossRefPubMedPubMedCentral
Metadata
Title
Intraurethral injection with LPS: an effective experimental model of prostatic inflammation
Authors
Fabiana Oliveira dos Santos Gomes
Amanda Costa Oliveira
Edlene Lima Ribeiro
Bruna Santos da Silva
Laise Aline Martins dos Santos
Ingrid Tavares de Lima
Amanda Karolina Soares e Silva
Shyrlene Meiry da Rocha Araújo
Terezinha Gonçalves
Mario Ribeiro de Melo-Junior
Christina Alves Peixoto
Publication date
01-01-2018
Publisher
Springer International Publishing
Published in
Inflammation Research / Issue 1/2018
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-017-1094-7

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