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Activation of innate anti-viral immune response genes in symptomatic benign prostatic hyperplasia.

Madigan AA, Sobek KM, Cummings JL, Green WR, Bacich DJ, O'Keefe DS - Genes Immun. (2012)

Bottom Line: We determined the expression of genes involved in the innate anti-viral immune response in tissues from patients undergoing surgery to alleviate the symptoms of BPH, and compared the results with prostate tissue with histologic BPH, but from patients with few urinary issues (asymptomatic BPH).We found that expression of complement factor I, apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like protein 3G, oligoadenylate synthetase 2 and interferon-induced tetratricopeptide 1, four genes whose protein products are involved in the innate anti-viral immune response, was significantly transcriptionally upregulated in symptomatic BPH.Additionally, we observe hypomethylation and concomitant expression of ancient retroviral-like sequences, the long interspersed nuclear element 1 retrotransposons, in symptomatic BPH when compared with normal prostate tissue.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15232, USA.

ABSTRACT
Benign prostatic hyperplasia (BPH) is the most common urologic disease in men over age 50. Symptoms include acute urinary retention, urgency to urinate and nocturia. For patients with severe symptoms, surgical treatment is used to remove the affected tissue. Interestingly, the presence of histologic BPH does not always correlate with symptoms. The molecular basis of symptomatic BPH and how it differs from asymptomatic BPH is unknown. Investigation into the molecular players involved in symptomatic BPH will likely give insight into novel therapeutic, and potentially preventative, targets. We determined the expression of genes involved in the innate anti-viral immune response in tissues from patients undergoing surgery to alleviate the symptoms of BPH, and compared the results with prostate tissue with histologic BPH, but from patients with few urinary issues (asymptomatic BPH). We found that expression of complement factor I, apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like protein 3G, oligoadenylate synthetase 2 and interferon-induced tetratricopeptide 1, four genes whose protein products are involved in the innate anti-viral immune response, was significantly transcriptionally upregulated in symptomatic BPH. Additionally, we observe hypomethylation and concomitant expression of ancient retroviral-like sequences, the long interspersed nuclear element 1 retrotransposons, in symptomatic BPH when compared with normal prostate tissue. These findings merit further investigation into the anti-viral immune response in symptomatic BPH.

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a. LINE1ORF2 real time PCR for symptomatic BPH, asymptomatic BPH and normal prostate tissue from organ donors. The Mann-Whitney statistical test was performed, determining that a statistically significant difference exists between symptomatic BPH and donors (p = 0.015), however there is no statistically significant difference between symptomatic and asymptomatic BPH.
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Figure 5: a. LINE1ORF2 real time PCR for symptomatic BPH, asymptomatic BPH and normal prostate tissue from organ donors. The Mann-Whitney statistical test was performed, determining that a statistically significant difference exists between symptomatic BPH and donors (p = 0.015), however there is no statistically significant difference between symptomatic and asymptomatic BPH.

Mentions: After observing the activation of an innate antiviral immune response in symptomatic BPH, we wanted to determine the mechanism potentially causing this response. Since we know that LINE-1 is demethylated in symptomatic BPH samples, we hypothesized that LINE-1 retroelements were being expressed and activating the anti-viral immune response in symptomatic BPH. Examination of LINE1ORF2 (LINE-1 open reading frame 2) expression in symptomatic BPH samples compared to donors demonstrates that there is a statistically significant difference in LINE-1 expression between symptomatic BPH (n = 19) and donor tissue (n = 8) (Figure 5; p = 0.015, Mann-Whitney). Examination of asymptomatic BPH samples (n = 14) indicates that the mean was lower than the symptomatic BPH mean but did not reach statistical significance (Figure 5). Again, LINE-1 expression in asymptomatic BPH may be due to the field defect observed in prostate cancer.


Activation of innate anti-viral immune response genes in symptomatic benign prostatic hyperplasia.

Madigan AA, Sobek KM, Cummings JL, Green WR, Bacich DJ, O'Keefe DS - Genes Immun. (2012)

a. LINE1ORF2 real time PCR for symptomatic BPH, asymptomatic BPH and normal prostate tissue from organ donors. The Mann-Whitney statistical test was performed, determining that a statistically significant difference exists between symptomatic BPH and donors (p = 0.015), however there is no statistically significant difference between symptomatic and asymptomatic BPH.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3475748&req=5

Figure 5: a. LINE1ORF2 real time PCR for symptomatic BPH, asymptomatic BPH and normal prostate tissue from organ donors. The Mann-Whitney statistical test was performed, determining that a statistically significant difference exists between symptomatic BPH and donors (p = 0.015), however there is no statistically significant difference between symptomatic and asymptomatic BPH.
Mentions: After observing the activation of an innate antiviral immune response in symptomatic BPH, we wanted to determine the mechanism potentially causing this response. Since we know that LINE-1 is demethylated in symptomatic BPH samples, we hypothesized that LINE-1 retroelements were being expressed and activating the anti-viral immune response in symptomatic BPH. Examination of LINE1ORF2 (LINE-1 open reading frame 2) expression in symptomatic BPH samples compared to donors demonstrates that there is a statistically significant difference in LINE-1 expression between symptomatic BPH (n = 19) and donor tissue (n = 8) (Figure 5; p = 0.015, Mann-Whitney). Examination of asymptomatic BPH samples (n = 14) indicates that the mean was lower than the symptomatic BPH mean but did not reach statistical significance (Figure 5). Again, LINE-1 expression in asymptomatic BPH may be due to the field defect observed in prostate cancer.

Bottom Line: We determined the expression of genes involved in the innate anti-viral immune response in tissues from patients undergoing surgery to alleviate the symptoms of BPH, and compared the results with prostate tissue with histologic BPH, but from patients with few urinary issues (asymptomatic BPH).We found that expression of complement factor I, apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like protein 3G, oligoadenylate synthetase 2 and interferon-induced tetratricopeptide 1, four genes whose protein products are involved in the innate anti-viral immune response, was significantly transcriptionally upregulated in symptomatic BPH.Additionally, we observe hypomethylation and concomitant expression of ancient retroviral-like sequences, the long interspersed nuclear element 1 retrotransposons, in symptomatic BPH when compared with normal prostate tissue.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15232, USA.

ABSTRACT
Benign prostatic hyperplasia (BPH) is the most common urologic disease in men over age 50. Symptoms include acute urinary retention, urgency to urinate and nocturia. For patients with severe symptoms, surgical treatment is used to remove the affected tissue. Interestingly, the presence of histologic BPH does not always correlate with symptoms. The molecular basis of symptomatic BPH and how it differs from asymptomatic BPH is unknown. Investigation into the molecular players involved in symptomatic BPH will likely give insight into novel therapeutic, and potentially preventative, targets. We determined the expression of genes involved in the innate anti-viral immune response in tissues from patients undergoing surgery to alleviate the symptoms of BPH, and compared the results with prostate tissue with histologic BPH, but from patients with few urinary issues (asymptomatic BPH). We found that expression of complement factor I, apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like protein 3G, oligoadenylate synthetase 2 and interferon-induced tetratricopeptide 1, four genes whose protein products are involved in the innate anti-viral immune response, was significantly transcriptionally upregulated in symptomatic BPH. Additionally, we observe hypomethylation and concomitant expression of ancient retroviral-like sequences, the long interspersed nuclear element 1 retrotransposons, in symptomatic BPH when compared with normal prostate tissue. These findings merit further investigation into the anti-viral immune response in symptomatic BPH.

Show MeSH
Related in: MedlinePlus