Given the emergence of P. acnes as an infecting agent in prostate tissue [7–9] we investigated the effect of the bacterium on prostate epithelial cells of non-malignant origin (RWPE-1). In vitro, P. acnes induced considerable secretion of IL-6 and IL-8 and, to a lesser extent, GM-CSF. Secretion of IL8 was shown to be mediated via TLR2, as the receptor blockage with anti-TLR2 monoclonal antibodies reduced its secretion. In contrast, we did not

observe any significant reduction in secretion of IL-6 and GM-CSF by blockage of TLR2. Earlier reports present evidence that P. acnes is able to stimulate monocytes and endothelial cells to secrete pro-inflammatory cytokines via activation of TLR2 [10, 11]. Our results partly confirm this. Even toll-like receptors 4 and 9 have been implicated in P. acnes mediated immune modulatory effects [20]. Both human and rat prostate epithelial cell Imatinib solubility dmso lines are known to express TLR2, TLR4, Autophagy phosphorylation and TLR9 [21, 22] and since blockage of TLR2 in our experiment has not totally inhibited cytokine secretion, the involvement of other TLR may also be hypothesized. However, possible TLR4 involvement is compromised by the observed downregulation of the gene expression. Another mechanism may involve auto inducing

capability of the released cytokines that generates a self-perpetuating inflammatory process. The increased secretion of such cytokines was accompanied by concordant mRNA up-regulation. Moreover, the broader analysis of inflammation associated genes revealed that chemokine ligands and pro-inflammatory substances CCL2, CXCL10, TNF-α, TNF-β (lymphotoxin-α), CSF3, IL1-α, and IFN-β were also significantly upregulated. Further studies are required to determine if upregulation of aforementioned genes is accompanied by enhanced cytokine production by prostate epithelial cells. The upregulation of the transcriptional regulators JUN, REL, RIPK2, Thiamet G NFKB2, NFKBIA,

IRF1, IRAK2 and the TLR/IL1-receptor co-factor TICAM1 is coherent with earlier studies of TLR2 signaling cascade leading to Fib activation [23, 24]. Secretion of IL-6, IL-8 and GM-CSF are central for recruitment and differentiation of macrophages and neutrophils in inflamed tissue [25–27]. A prolonged time of increased cytokine levels might have adverse effects on the tissue. P. acnes induced elevation of IL-8 expression in hair-follicle endothelial cells is associated with epidermal hyperplasia and follicular hyperkeratosis in acne vulgaris and psoriasis [28, 29]. There is also a correlation between the more pronounced IL-8 expression and dermal angiogenesis [29]. Interestingly, both IL-6 and IL-8 have been suggested as contributors to prostate cancer development. The expression of IL-6 and its receptor has been demonstrated in clinical specimens of both prostate cancer and benign prostate hyperplasia [30], and levels of IL-6 increase in organ-confined tumors [31].