Testosterone suppresses uropathogenic Escherichia coli invasion and colonization within prostate cells and inhibits inflammatory responses through JAK/STAT-1 signaling pathway

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4 引文 (Scopus)

摘要

Prostatitis is a common condition in adult men of all ages. Uropathogenic Escherichia coli (UPEC) are most frequent pathogen involved in bacterial prostatitis by refluxing the infected urine into prostatic ducts and resulting in an ascending urethral infection. However, the study about the mechanisms of UPEC to invade, replicate and persist in normal prostate epithelial cell is only few. Given the fact that UPEC is pathogen most frequently involved in prostatitis and that testosterone has been demonstrated to attenuate prostate inflammation caused by other etiologies. In this study we investigated whether the testosterone reduces the prostatitis and related mechanism by regulating IFN-?/STAT1 signaling pathway. In the current study aimed to clarify whether testosterone influences the process of UPEC-induced prostate inflammation and invasion into the prostate epithelial cells. In addition, we set up a normal prostate cell model for UPEC infection to evaluate the ability to invade the urothelial cells as well as the colonization of intercellular bacterial communities in vitro. By using the model, we examine the effects of testosterone to suppress effectively the invasion and survival of UPEC in the prostate cells, and inhibit LPS-induced inflammatory responses through the JAK/STAT1 pathway have also been indicated. Our results demonstrated testosterone not only suppressed the invasion and colonization of UPEC, but also inhibited the expression of pro-inflammatory IL-1ß, IL-6 and IL-8 cytokines expression induced by UPEC in a dose-dependent manner. We found the effective dose of testosterone to suppress UPEC infect prostate cells may be appropriate under 40µg/ml. Our data also revealed 20µg/ml testosterone treated PZ-HPV-7 cells significantly suppressed the LPS-induced JAK/STAT1 pathway and inflammatory responses, and reached to maximal effects at 40µg/ml treatment. These results indicate that testosterone plays an anti-inflammatory role in LPS-induced prostate cell inflammation by down-regulating JAK/STAT1 signaling pathway. Interestingly, the JAK inhibitor and testosterone for 24hr pretreatment rather markedly induced the colonization of UPEC in the PZ-HPV-7 cells. Based on the above data, the suppression of UPEC colonization in the prostate cells by testosterone seems to be unrelated with JAK/STAT signaling pathway, whereas the JAK may involve into the UPEC infection. Summing up these data, our findings have demonstrated the suppressive effects of testosterone on the invasion and survival of UPEC and induced inflammation in prostate epithelial cells. These findings indicate the action mechanism of testosterone as an anti-inflammatory mediator in the prostate cells is regulated through JAK/STAT1 signaling pathway, may be beneficial in treating prostate inflammation. Altogether, this study has provided the possibility that using testosterone in the prevention and clinical treatment of prostatitis is a new direction.
原文英語
文章編號e0180244
期刊PLoS One
12
發行號6
DOIs
出版狀態已發佈 - 六月 1 2017

指紋

uropathogenic Escherichia coli
Uropathogenic Escherichia coli
Escherichia coli
testosterone
Testosterone
Prostate
inflammation
prostatitis
Prostatitis
cells
Human papillomavirus 7
Inflammation
Escherichia coli Infections
epithelial cells
Epithelial Cells
Pathogens
Anti-Inflammatory Agents
infection
pathogens
interleukin-8

ASJC Scopus subject areas

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

引用此文

@article{38f2a862c6104c7fbedbab91a4246322,
title = "Testosterone suppresses uropathogenic Escherichia coli invasion and colonization within prostate cells and inhibits inflammatory responses through JAK/STAT-1 signaling pathway",
abstract = "Prostatitis is a common condition in adult men of all ages. Uropathogenic Escherichia coli (UPEC) are most frequent pathogen involved in bacterial prostatitis by refluxing the infected urine into prostatic ducts and resulting in an ascending urethral infection. However, the study about the mechanisms of UPEC to invade, replicate and persist in normal prostate epithelial cell is only few. Given the fact that UPEC is pathogen most frequently involved in prostatitis and that testosterone has been demonstrated to attenuate prostate inflammation caused by other etiologies. In this study we investigated whether the testosterone reduces the prostatitis and related mechanism by regulating IFN-?/STAT1 signaling pathway. In the current study aimed to clarify whether testosterone influences the process of UPEC-induced prostate inflammation and invasion into the prostate epithelial cells. In addition, we set up a normal prostate cell model for UPEC infection to evaluate the ability to invade the urothelial cells as well as the colonization of intercellular bacterial communities in vitro. By using the model, we examine the effects of testosterone to suppress effectively the invasion and survival of UPEC in the prostate cells, and inhibit LPS-induced inflammatory responses through the JAK/STAT1 pathway have also been indicated. Our results demonstrated testosterone not only suppressed the invasion and colonization of UPEC, but also inhibited the expression of pro-inflammatory IL-1{\ss}, IL-6 and IL-8 cytokines expression induced by UPEC in a dose-dependent manner. We found the effective dose of testosterone to suppress UPEC infect prostate cells may be appropriate under 40µg/ml. Our data also revealed 20µg/ml testosterone treated PZ-HPV-7 cells significantly suppressed the LPS-induced JAK/STAT1 pathway and inflammatory responses, and reached to maximal effects at 40µg/ml treatment. These results indicate that testosterone plays an anti-inflammatory role in LPS-induced prostate cell inflammation by down-regulating JAK/STAT1 signaling pathway. Interestingly, the JAK inhibitor and testosterone for 24hr pretreatment rather markedly induced the colonization of UPEC in the PZ-HPV-7 cells. Based on the above data, the suppression of UPEC colonization in the prostate cells by testosterone seems to be unrelated with JAK/STAT signaling pathway, whereas the JAK may involve into the UPEC infection. Summing up these data, our findings have demonstrated the suppressive effects of testosterone on the invasion and survival of UPEC and induced inflammation in prostate epithelial cells. These findings indicate the action mechanism of testosterone as an anti-inflammatory mediator in the prostate cells is regulated through JAK/STAT1 signaling pathway, may be beneficial in treating prostate inflammation. Altogether, this study has provided the possibility that using testosterone in the prevention and clinical treatment of prostatitis is a new direction.",
author = "Ho, {Chen Hsun} and Fan, {Chia Kwung} and Yu, {Hong Jeng} and Wu, {Chia Chang} and Chen, {Kuan Chou} and Liu, {Shih Ping} and Cheng, {Po Ching}",
year = "2017",
month = "6",
day = "1",
doi = "10.1371/journal.pone.0180244",
language = "English",
volume = "12",
journal = "PLoS One",
issn = "1932-6203",
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T1 - Testosterone suppresses uropathogenic Escherichia coli invasion and colonization within prostate cells and inhibits inflammatory responses through JAK/STAT-1 signaling pathway

AU - Ho, Chen Hsun

AU - Fan, Chia Kwung

AU - Yu, Hong Jeng

AU - Wu, Chia Chang

AU - Chen, Kuan Chou

AU - Liu, Shih Ping

AU - Cheng, Po Ching

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Prostatitis is a common condition in adult men of all ages. Uropathogenic Escherichia coli (UPEC) are most frequent pathogen involved in bacterial prostatitis by refluxing the infected urine into prostatic ducts and resulting in an ascending urethral infection. However, the study about the mechanisms of UPEC to invade, replicate and persist in normal prostate epithelial cell is only few. Given the fact that UPEC is pathogen most frequently involved in prostatitis and that testosterone has been demonstrated to attenuate prostate inflammation caused by other etiologies. In this study we investigated whether the testosterone reduces the prostatitis and related mechanism by regulating IFN-?/STAT1 signaling pathway. In the current study aimed to clarify whether testosterone influences the process of UPEC-induced prostate inflammation and invasion into the prostate epithelial cells. In addition, we set up a normal prostate cell model for UPEC infection to evaluate the ability to invade the urothelial cells as well as the colonization of intercellular bacterial communities in vitro. By using the model, we examine the effects of testosterone to suppress effectively the invasion and survival of UPEC in the prostate cells, and inhibit LPS-induced inflammatory responses through the JAK/STAT1 pathway have also been indicated. Our results demonstrated testosterone not only suppressed the invasion and colonization of UPEC, but also inhibited the expression of pro-inflammatory IL-1ß, IL-6 and IL-8 cytokines expression induced by UPEC in a dose-dependent manner. We found the effective dose of testosterone to suppress UPEC infect prostate cells may be appropriate under 40µg/ml. Our data also revealed 20µg/ml testosterone treated PZ-HPV-7 cells significantly suppressed the LPS-induced JAK/STAT1 pathway and inflammatory responses, and reached to maximal effects at 40µg/ml treatment. These results indicate that testosterone plays an anti-inflammatory role in LPS-induced prostate cell inflammation by down-regulating JAK/STAT1 signaling pathway. Interestingly, the JAK inhibitor and testosterone for 24hr pretreatment rather markedly induced the colonization of UPEC in the PZ-HPV-7 cells. Based on the above data, the suppression of UPEC colonization in the prostate cells by testosterone seems to be unrelated with JAK/STAT signaling pathway, whereas the JAK may involve into the UPEC infection. Summing up these data, our findings have demonstrated the suppressive effects of testosterone on the invasion and survival of UPEC and induced inflammation in prostate epithelial cells. These findings indicate the action mechanism of testosterone as an anti-inflammatory mediator in the prostate cells is regulated through JAK/STAT1 signaling pathway, may be beneficial in treating prostate inflammation. Altogether, this study has provided the possibility that using testosterone in the prevention and clinical treatment of prostatitis is a new direction.

AB - Prostatitis is a common condition in adult men of all ages. Uropathogenic Escherichia coli (UPEC) are most frequent pathogen involved in bacterial prostatitis by refluxing the infected urine into prostatic ducts and resulting in an ascending urethral infection. However, the study about the mechanisms of UPEC to invade, replicate and persist in normal prostate epithelial cell is only few. Given the fact that UPEC is pathogen most frequently involved in prostatitis and that testosterone has been demonstrated to attenuate prostate inflammation caused by other etiologies. In this study we investigated whether the testosterone reduces the prostatitis and related mechanism by regulating IFN-?/STAT1 signaling pathway. In the current study aimed to clarify whether testosterone influences the process of UPEC-induced prostate inflammation and invasion into the prostate epithelial cells. In addition, we set up a normal prostate cell model for UPEC infection to evaluate the ability to invade the urothelial cells as well as the colonization of intercellular bacterial communities in vitro. By using the model, we examine the effects of testosterone to suppress effectively the invasion and survival of UPEC in the prostate cells, and inhibit LPS-induced inflammatory responses through the JAK/STAT1 pathway have also been indicated. Our results demonstrated testosterone not only suppressed the invasion and colonization of UPEC, but also inhibited the expression of pro-inflammatory IL-1ß, IL-6 and IL-8 cytokines expression induced by UPEC in a dose-dependent manner. We found the effective dose of testosterone to suppress UPEC infect prostate cells may be appropriate under 40µg/ml. Our data also revealed 20µg/ml testosterone treated PZ-HPV-7 cells significantly suppressed the LPS-induced JAK/STAT1 pathway and inflammatory responses, and reached to maximal effects at 40µg/ml treatment. These results indicate that testosterone plays an anti-inflammatory role in LPS-induced prostate cell inflammation by down-regulating JAK/STAT1 signaling pathway. Interestingly, the JAK inhibitor and testosterone for 24hr pretreatment rather markedly induced the colonization of UPEC in the PZ-HPV-7 cells. Based on the above data, the suppression of UPEC colonization in the prostate cells by testosterone seems to be unrelated with JAK/STAT signaling pathway, whereas the JAK may involve into the UPEC infection. Summing up these data, our findings have demonstrated the suppressive effects of testosterone on the invasion and survival of UPEC and induced inflammation in prostate epithelial cells. These findings indicate the action mechanism of testosterone as an anti-inflammatory mediator in the prostate cells is regulated through JAK/STAT1 signaling pathway, may be beneficial in treating prostate inflammation. Altogether, this study has provided the possibility that using testosterone in the prevention and clinical treatment of prostatitis is a new direction.

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