Propionibacterium acnes infection induces upregulation of inflammatory genes and cytokine secretion in prostate epithelial cells

Department of Clinical Microbiology/Virology, Umeå University, SE-901 87 Umeå, Sweden.
BMC Microbiology (Impact Factor: 2.73). 04/2010; 10(1):126. DOI: 10.1186/1471-2180-10-126
Source: PubMed


The immune stimulating bacterium Propionibacterium acnes is a frequent colonizer of benign and malignant prostate tissue. To understand the pathogenesis of the earliest phase of this infection, we examined the P. acnes triggered immune response in cultivated prostate epithelial cells.
Prostate epithelial cells are triggered to secrete IL-6, IL-8 and GM-CSF when infected with P. acnes. The secretion of cytokines is accompanied by NFkappaB related upregulation of the secreted cytokines as well as several components of the TLR2-NFkappaB signaling pathway.
P. acnes has potential to trigger a strong immune reaction in the prostate glandular epithelium. Upon infection of prostate via the retrograde urethral route, the induced inflammatory reaction might facilitate bacterial colonization deeper in the prostate tissue where persistent inflammation may impact the development of prostate diseases as hyperplasia and/or malignancy.

Download full-text


Available from: Jan Olsson
  • Source
    • "Serum titres of P. acnes antibodies correlate positively with PSA in cancer-negative patients [15], thus indicating P. acnes involvement in prostatic inflammation. Furthermore, P. acnes has been shown to be associated with histological inflammation in human prostatectomy specimens [13] and to induce a strong inflammatory response in prostate derived tissue culture models [14], [16]. However, well-characterized models of acute and chronic prostate infection are yet to be developed. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Chronic inflammation in the prostate, seen as infiltration of inflammatory cells into the prostate gland in histological samples, affects approximately half the male population without indication of prostate disease, and is almost ubiquitous in patients diagnosed with benign prostate hyperplasia and cancer. Several studies have demonstrated the Gram-positive bacterium Propionibacterium acnes to be frequently present in prostate tissue from men suffering from prostate disease. P. acnes has been shown to be associated with histological inflammation in human prostatectomy specimens, and also to induce strong inflammatory response in prostate-derived tissue culture models. The present paper describes a rat model for assessment of the pathogenic potential of P. acnes in prostate. Prostate glands of Sprague Dawley rats (n = 98) were exposed via an abdominal incision and live P. acnes or, in control rats, saline were injected into the ventral and dorso-lateral lobes. Rats were sacrificed 5 days, 3 weeks, 3 months and 6 months post infection, and prostate tissue was analyzed for bacterial content and histological inflammation. Rat sera were assessed for levels of CRP and anti-P. acnes IgG. Live P. acnes could be recovered from the dorso-lateral lobes up to 3 months post infection, while the ventral lobes were cleared from bacteria at that time. In samples up to 3 months post infection, the dorso-lateral lobes exhibited intense focal inflammation. CRP and IgG levels were elevated throughout the span of the experiment, and reached maximum levels 3 weeks and 3 months post infection, respectively. We show that P. acnes have the potential to cause chronic infection in previously healthy prostate, and that the infection has potential to cause chronic histological inflammation in the infected tissue. The high prevalence of P. acnes in human prostate tissue calls for resolution of pathogenic details. The present rat model suggests that complications such as chronic inflammation may be induced by P. acnes infection.
    Full-text · Article · Dec 2012 · PLoS ONE
  • Source
    • "IL-6 is a multifunctional inflammatory cytokine that regulates chronic inflammation and can create a cellular microenvironment beneficial to cancer growth2930. Prostate epithelial cells can produce IL-8 and IL-6 in response to bacterial infections with microbes such as Propionibacterium and Mycoplasma[18,31]. To determine whether Nod1 and Nod2 can promote the production of proinflammatory cytokines or chemokines in prostate epithelial cells, we examined IL-8/KC and IL-6 production in PC3, DU145, and TRAMP-C2 cells in response to Tri- DAP and MDP. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Nod1 and Nod2 are cytosolic receptors which are responsible for sensing bacterial peptidoglycan derivatives. In this study, we determined whether Nod1 and Nod2 are involved in the innate immune responses of prostate epithelial cells. The expression of Nod1 and Nod2 was examined by RT-PCR and immunohistochemistry. ELISA was performed to determine the production of cytokines/chemokines. Activation of NF-κB and MAPK was examined using western blot analysis. The Nod1 gene was distinctly expressed in all tested cells including DU145, PC3, and TRAMP-C2 cells, whereas Nod2 expression was weak. Both Nod1 and Nod2 proteins were expressed in normal mouse prostate epithelia with difference of expression levels. Tri-DAP (Nod1 agonist), but not MDP (Nod2), increased the production of IL-8 (or KC) and IL-6 in prostate epithelial cells. Tri-DAP and MDP could upregulate the gene expression of COX-2 and activate NF-κB and MAPK. In addition, Tri-DAP and MDP synergized with TLR agonists to induce the production of IL-8/KC or IL-6 in PC3 and TRAMP-C2 cells. We finally showed that Nod1 and Nod2 were also expressed in a wide range of prostate lesions including prostate intraepithelial neoplasm (PIN), phyllodes-like tumor, and adenocarcinoma in TRAMP (transgenic adenocarcinoma of the mouse prostate) mice, even though the expression level of Nod1 and Nod2 was different. These results indicate that Nod1 and Nod2 may play important roles in the innate immune response of prostate epithelial cells and the development and progression of prostate cancer.
    Full-text · Article · Sep 2012 · The Prostate
  • Source
    • "P. acnes was found to be associated with histological inflammation in the prostate, and we, along with others, detected it in cancerous prostates (Cohen et al., 2005; Alexeyev et al., 2007; Fassi Fehri et al., 2011). Investigations with prostate epithelial cells showed that P. acnes induced the secretion of cytokines and chemokines such as IL-6, IL-8 and GM-CSF (Drott et al., 2010; Fassi Fehri et al., 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The contribution of the human microbiota to health and disease is poorly understood. Propionibacterium acnes is a prominent member of the skin microbiota, but is also associated with acne vulgaris. This bacterium has gained recent attention as a potential opportunistic pathogen at non-skin infection sites due to its association with chronic pathologies and its isolation from diseased prostates. We performed comparative global-transcriptional analyses for P. acnes infection of keratinocytes and prostate cells. P. acnes induced an acute, transient transcriptional inflammatory response in keratinocytes, whereas this response was delayed and sustained in prostate cells. We found that P. acnes invaded prostate epithelial cells, but not keratinocytes, and was detectable intracellularly 7 days post infection. Further characterization of the host cell response to infection revealed that vimentin was a key determinant for P. acnes invasion in prostate cells. siRNA-mediated knock-down of vimentin in prostate cellsattenuated bacterial invasion and the inflammatory response to infection. We conclude that host cell tropism, which may depend on the host protein vimentin, is relevant for P. acnes invasion and in part determines its sustained inflammatory capacity and persistence of infection.
    Full-text · Article · Jul 2012 · Cellular Microbiology
Show more

We use cookies to give you the best possible experience on ResearchGate. Read our cookies policy to learn more.