Abstract

Benign prostatic hyperplasia (BPH) is the most common urologic disease among elderly men. A well-established in vitro cell model is required to determine the therapeutic mechanism of BPH inflammation. In this study, we attempted to establish an immortalized human prostate stromal cell line by transfecting with HPV-16 E6/E7 and designated as ihPSC. No significant difference was found in fibroblast-like morphology between primary hPSC and ihPSC. The ihPSC possessed a significantly higher cell proliferation rate than primary hPSC. The prostatespecific markers and proteins including cytoskeleton (α-SMA and vimentin) and smooth muscle (calponin), especially the androgen receptor (AR) were also examined in ihPSC, almost identical to the primary hPSC. To create an in vitro model featuring chronic prostatic inflammation, ihPSC was stimulated with IFN-y+IL-17 and then treated with the high molecular weight hyaluronic acid hylan G-F 20 as an alternative strategy for inhibiting BPH inflammation. Hylan G-F 20 could dose-dependently diminish the inflammation-induced proliferation in ihPSC. The enhanced expressions of inflammatory molecules including IL-1β, IL-6, IL-8, cyclooxygenase 2 (COX2), inducible nitrogen oxide synthase (iNOS), and Toll-like receptor 4 (TLR4) were all abolished by hylan G-F 20. For inflammatory signaling, hylan G-F 20 can also diminish the IFN-y+IL-17-increased expression of iNOS and p65 in ihPSC. These findings suggest that ihPSC could provide a mechanism-based platform for investigating prostate inflammation. The hylan G-F 20 showed strong anti-inflammatory effects by decreasing inflammatory cytokines and signalings in the ihPSC, indicating its therapeutic potentials in BPH treatment in the future.

Original languageEnglish
Article numbere0178152
JournalPLoS One
Volume12
Issue number5
DOIs
Publication statusPublished - May 1 2017

Fingerprint

hyaluronic acid
stromal cells
Hyaluronic Acid
Stromal Cells
Prostatic Hyperplasia
Prostate
hyperplasia
inflammation
Cells
cell lines
Inflammation
Cell Line
nitrogen oxides
Interleukin-17
Nitric Oxide
Human papillomavirus 16
urinary tract diseases
Urologic Diseases
therapeutics
Toll-Like Receptor 4

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Inhibition of chronic prostate inflammation by hyaluronic acid through an immortalized human prostate stromal cell line model. / Liu, Che Ming; Chen, Wei Hong; Chiou, Chi Sheng; Lo, Wen Cheng; Dubey, Navneet Kumar; Chen, Yu Chin; Lai, Wen Fu T.; Yeh, Shauh Der; Chiang, Han Sun; Deng, Win Ping.

In: PLoS One, Vol. 12, No. 5, e0178152, 01.05.2017.

Research output: Contribution to journalArticle

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author = "Liu, {Che Ming} and Chen, {Wei Hong} and Chiou, {Chi Sheng} and Lo, {Wen Cheng} and Dubey, {Navneet Kumar} and Chen, {Yu Chin} and Lai, {Wen Fu T.} and Yeh, {Shauh Der} and Chiang, {Han Sun} and Deng, {Win Ping}",
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AU - Chen, Wei Hong

AU - Chiou, Chi Sheng

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AU - Dubey, Navneet Kumar

AU - Chen, Yu Chin

AU - Lai, Wen Fu T.

AU - Yeh, Shauh Der

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AU - Deng, Win Ping

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AB - Benign prostatic hyperplasia (BPH) is the most common urologic disease among elderly men. A well-established in vitro cell model is required to determine the therapeutic mechanism of BPH inflammation. In this study, we attempted to establish an immortalized human prostate stromal cell line by transfecting with HPV-16 E6/E7 and designated as ihPSC. No significant difference was found in fibroblast-like morphology between primary hPSC and ihPSC. The ihPSC possessed a significantly higher cell proliferation rate than primary hPSC. The prostatespecific markers and proteins including cytoskeleton (α-SMA and vimentin) and smooth muscle (calponin), especially the androgen receptor (AR) were also examined in ihPSC, almost identical to the primary hPSC. To create an in vitro model featuring chronic prostatic inflammation, ihPSC was stimulated with IFN-y+IL-17 and then treated with the high molecular weight hyaluronic acid hylan G-F 20 as an alternative strategy for inhibiting BPH inflammation. Hylan G-F 20 could dose-dependently diminish the inflammation-induced proliferation in ihPSC. The enhanced expressions of inflammatory molecules including IL-1β, IL-6, IL-8, cyclooxygenase 2 (COX2), inducible nitrogen oxide synthase (iNOS), and Toll-like receptor 4 (TLR4) were all abolished by hylan G-F 20. For inflammatory signaling, hylan G-F 20 can also diminish the IFN-y+IL-17-increased expression of iNOS and p65 in ihPSC. These findings suggest that ihPSC could provide a mechanism-based platform for investigating prostate inflammation. The hylan G-F 20 showed strong anti-inflammatory effects by decreasing inflammatory cytokines and signalings in the ihPSC, indicating its therapeutic potentials in BPH treatment in the future.

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