The vitamin D receptor agonist elocalcitol inhibits IL‐8‐dependent benign prostatic hyperplasia stromal cell proliferation and inflammatory response by targeting the RhoA/Rho kinase and NF‐kB pathways

Abstract

These data provide a mechanistic explanation for the anti-proliferative and anti-inflammatory properties of elocalcitol in BPH cells.

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

“…There is also evidence that a loss of tolerance to self-antigens, associated with expansion of Th17 cells and IL17 overexpression, is crucial in BPH development (Steiner et al 2003b). This is also supported by the observation that IL8 and IL6, key executors of stromal growth in BPH, are produced by prostatic stromal cells in response to IL17 (Penna et al 2009), thus linking a self-perpetuating autoimmune response to altered tissue remodeling and hyperplastic growth (Ropiquet et al 1999).…”

“…After 24 h of serum starvation, cells were incubated with DHT (30 nM) or left untreated for 24 h, then were stimulated or not with TNFa (10 ng/ml) or with LPS (100 ng/ml) for 5 h. Cells cultured in phenol red and serum-free medium were used as control. Immunostaining was performed as previously described (Penna et al 2009) using primary Abs against NF-kB p65 (1:100) followed by Alexa Fluor conjugated secondary Abs (1:200). Slides were then treated as reported elsewhere (Penna et al 2009) and examined with a phase contrast microscope (Nikon Microphot-FX microscope, Nikon, Tokyo, Japan).…”

“…Immunostaining was performed as previously described (Penna et al 2009) using primary Abs against NF-kB p65 (1:100) followed by Alexa Fluor conjugated secondary Abs (1:200). Slides were then treated as reported elsewhere (Penna et al 2009) and examined with a phase contrast microscope (Nikon Microphot-FX microscope, Nikon, Tokyo, Japan). Experiments were performed three times with different cell preparations.…”

“…BPH cells have been previously described to act as antigen-presenting cells (APCs; Penna et al 2009), thus indicating their potential role in inducing and sustaining an autoimmune response within the prostatic gland. Histological analysis of inflammatory cell infiltrates in prostatectomy specimens from a cohort of BPH patients and their correlation with preoperatory serum testosterone levels were also performed.…”

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

“…Immunohistochemical studies were performed with slight modifications of previously described protocols (Penna et al 2009). Briefly, prostate sections were incubated overnight at 4 8C or with the monoclonal mouse anti-CD45 (1:100 vol/ vol, DakoCytomation, Copenhagen, Denmark), the antimacrophage antibody RAM11 (Dako, Carpenteria, CA, USA; 1:80 vol/vol), or anti-lactoferrin (1:1000 vol/vol, Sigma) as primary antibodies.…”