Toll-Like Receptor 4 in Rat Prostate: Modulation by Testosterone and Acute Bacterial Infection in Epithelial and Stromal Cells1

Abstract

The prostate gland is the most inflammation-prone organ in the male reproductive tract. However, little information is available regarding the immunobiology of this gland. Toll-like receptor 4 (TLR4) is considered to be a major sensor of danger signals and a key trigger of the innate immune responses. TLRs have also been implicated in the development of different inflammatory diseases in organs in which epithelial-stromal interactions are critical for homeostasis. The purpose of this work was to evaluate the presence and regulation of TLR4 in the rat prostate. Western blot and immunocytochemical studies revealed that constitutive expression of TLR4 in the rat ventral prostate was localized in the epithelial cells, mainly associated with the rough endoplasmic reticulum, as well as in smooth muscle cells in the stroma. In addition, increased concentrations of TLR4 were found in castrated rats, predominantly in hypertrophied smooth muscle cells. On the other hand, using a bacterial prostatitis model, we observed an increment in the TLR4 cytoplasmic content and migration of this receptor to the apical plasmatic membranes of epithelial cells at 24 h and 48 h post-infection. These findings suggest that the prostate gland is able to recognize pathogens and to initiate immune responses. In addition, TLR4 appears to be implicated in the vital stromal-epithelial interactions that maintain prostate homeostasis during prostatitis, as well as following androgen deprivation.

Testosterone protects from metabolic syndrome-associated prostate inflammation: an experimental study in rabbit

“…An anti-inflammatory effect of testosterone in castration-induced prostate inflammation was previously reported (Robinette 1988, Tangbanluekal & Robinette 1993, Quintar et al 2006, Yatkin et al 2009). Androgens therefore act as endogenous inhibitors of immune responses, even in the prostate, as already reported for other autoimmune processes (Ansar Ahmed et al 1986, Fox 1992, Harbuz et al 1995, Fijak et al 2011.…”

Antiinflammatory effect of androgen receptor activation in human benign prostatic hyperplasia cells

“…A possible hormonal basis for prostate inflammation is suggested by preclinical studies in animal models, demonstrating that hypogonadism induced surgically (Robinette 1988, Desai et al 2004, Quintar et al 2006, Meng et al 2011 or by HFD administration ) exacerbate prostate inflammation and that exogenous testosterone can counteract this effect. In particular, we have shown in a rabbit model that testosterone supplementation can prevent HFD-induced prostatic alterations, including inflammation, tissue remodeling, and hypoxia .…”

Immunomodulatory effects of testosterone evaluated in all-trans retinoic acid differentiated HL-60 cells, granulocytes, and monocytes

“…[4][5]. A possible reason for this may be that testosterone down-regulates expression of Toll-like receptor 4 (TLR4) [53], which mediates LPS signaling in immune cells [54,55]. This has been illustrated in human endothelial cells treated with dihydrotestosterone for 4 hours [56] and murine macrophages exposed to testosterone for 12-24 hours [57].…”