Testosterone abrogates TLR4 activation in prostate smooth muscle cells contributing to the preservation of a differentiated phenotype

Leimgruber, Carolina; Quintar, Amado A.; García, Luciana; Petiti, Juan Pablo; Paul, Ana Lucía De; Maldonado, Cristina A.

doi:10.1002/jcp.24314

Cited by 23 publications

(18 citation statements)

References 38 publications

(46 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TLR4 is also actively involved in bacterial invasion, and TLR4/cAMP-mediated immune function can expel UPEC from infected uroepithelial cells [35]. Leimgruber et al showed that the presence of testosterone could downregulate TLR4 activation and prevent the dedifferentiated (myofibroblast-like) phenotype of prostate smooth muscle cells stimulated by bacterial LPS [36, 37]. They also demonstrated that testosterone reduces cytokine secretion after LPS challenge, which is consistent with our results with UPEC-infected testosterone-treated cells.…”

Section: Discussionmentioning

confidence: 99%

“…Testosterone may reduce IL-6 and TNF-α production after LPS challenge by preventing Iκβ-alpha degradation and NF-κβ nuclear translocation [36]. Although the anti-inflammatory effects of testosterone in variety of tissues with microbial infection are well known, the mechanism of androgen action on prostate inflammatory response to bacterial LPS was not very clear.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Fan

et al. 2017

PLoS ONE

View full text Add to dashboard Cite

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-γ/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-1β, 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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Fan

et al. 2017

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Our studies have found that not only the epithelial but also stromal cells of the prostate express TLR4 both in vivo (Quintar et al, ; Gatti et al, ) and in vitro (Leimgruber et al, , ). Additional works have documented that all TLRs are expressed in prostatic stromal cells (Penna et al, ).…”

Section: Host Defense Molecules In the Prostate Glandmentioning

confidence: 82%

“…It has been reported that the stromal compartment critically influences the initiation and/or maintenance of proliferative pathologies in the prostate gland (Tuxhorn et al, ; Antonioli et al, ; Penna et al, ). Indeed, we described a rapid stromal response to bacterial infection, characterized mainly by hypertrophy and the acquisition of a secretory phenotype in smooth muscle cells (Quintar et al, ) which was then reproduced in vitro (Leimgruber et al, , , ). Related to this, much evidence suggests that smooth muscle cells are metabolically dynamic cells with the potential to express and secrete numerous highly active signaling proteins (Singer et al, ).…”

Section: Prostatic Inflammation and Its Impact On Prostatic Tissuesmentioning

confidence: 99%

Androgen regulation of host defenses and response to inflammatory stimuli in the prostate gland

Quintar

Maldonado

2017

Cell Biology International

View full text Add to dashboard Cite

The prostate gland is a strictly androgen-dependent organ which is also the main target of infectious and inflammatory diseases in the male reproductive tract. Host defenses and immunity of the gland have unique features to maintain a constant balance between response and tolerance to diverse antigens. In this context, the effects of reproductive hormones on the male tract are thus complex and have just started to be defined. From the classical description of "the prostatic antibacterial factor," many host defense proteins with potent microbicidal and anti-tumoral activities have been described in the organ. Indeed, it has been proposed a central role for resident cells, that is, epithelial and smooth muscle cells, in the prostatic response against injuries. However, these cells also represent the target of the inflammatory damage, leading to the development of a Proliferative Inflammatory Atrophy-like process in the epithelium and a myofibroblastic-like reactive stroma. Available data on androgen regulation of inflammation led to a model of the complex control, in which the final effect will depend on the tissue microenvironment, the cause of inflammation, and the levels of androgens among other factors. In this paper, we review the current scientific literature about the inflammatory process in the gland, the modulation of host defense proteins, and the influence of testosterone on the resolution of prostatitis.

show abstract

“…They also extended the observations to determine the effects of castration, and showed that RELA (therein referred to as NFkB/p65), in combination with CD14 and MyD88, coordinates the adaptation of epithelial and smooth-muscle cells to androgen deprivation, including the ability to produce surfactant protein D (SP-D) [48], [49].…”

Section: Discussionmentioning

confidence: 93%

Transcription Factors Involved in Prostate Gland Adaptation to Androgen Deprivation

Rosa‐Ribeiro

Nishan

Vidal³

et al. 2014

PLoS ONE

View full text Add to dashboard Cite

Androgens regulate prostate physiology, and exert their effects through the androgen receptor. We hypothesized that androgen deprivation needs additional transcription factors to orchestrate the changes taking place in the gland after castration and for the adaptation of the epithelial cells to the androgen-deprived environment, ultimately contributing to the origin of castration-resistant prostate cancer. This study was undertaken to identify transcription factors that regulate gene expression after androgen deprivation by castration (Cas). For the sake of comparison, we extended the analysis to the effects of administration of a high dose of 17β-estradiol (E2) and a combination of both (Cas+E2). We approached this by (i) identifying gene expression profiles and enrichment terms, and by searching for transcription factors in the derived regulatory pathways; and (ii) by determining the density of putative transcription factor binding sites in the proximal promoter of the 10 most up- or down-regulated genes in each experimental group in comparison to the controls Gapdh and Tbp7. Filtering and validation confirmed the expression and localized EVI1 (Mecom), NFY, ELK1, GATA2, MYBL1, MYBL2, and NFkB family members (NFkB1, NFkB2, REL, RELA and RELB) in the epithelial and/or stromal cells. These transcription factors represent major regulators of epithelial cell survival and immaturity as well as an adaptation of the gland as an immune barrier in the absence of functional stimulation by androgens. Elk1 was expressed in smooth muscle cells and was up-regulated after day 4. Evi1 and Nfy genes are expressed in both epithelium and stroma, but were apparently not affected by androgen deprivation.

show abstract

Testosterone abrogates TLR4 activation in prostate smooth muscle cells contributing to the preservation of a differentiated phenotype

Cited by 23 publications

References 38 publications

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

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

Androgen regulation of host defenses and response to inflammatory stimuli in the prostate gland

Transcription Factors Involved in Prostate Gland Adaptation to Androgen Deprivation

Contact Info

Product

Resources

About