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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. IFIT1 real time PCR with symptomatic and asymptomatic BPH samples. The Mann-Whitney statistical test was utilized for statistical analysis and determined that there was no statistically significant difference between the two groups. b. Real time PCR for IFIT1 in symptomatic BPH and asymptomatic BPH samples in which the prostate mass was less than 60g. Statistical analysis using the Mann-Whitney rank-sum test demonstrates a statistically significant difference between the two groups, p = 0.0118.
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Figure 3: a. IFIT1 real time PCR with symptomatic and asymptomatic BPH samples. The Mann-Whitney statistical test was utilized for statistical analysis and determined that there was no statistically significant difference between the two groups. b. Real time PCR for IFIT1 in symptomatic BPH and asymptomatic BPH samples in which the prostate mass was less than 60g. Statistical analysis using the Mann-Whitney rank-sum test demonstrates a statistically significant difference between the two groups, p = 0.0118.

Mentions: In an attempt to distinguish activation of these genes in response to virus versus other pathogens, we examined the expression profile of interferon-induced tetratricopeptide 1 (IFIT1). IFIT1 expression is activated in response to viruses as well as IFNalpha/beta, which are induced in response to virus. The function of IFIT1 is to inhibit cellular and viral processes such as translation, migration, proliferation, signaling and viral replication.13 Real time PCR for IFIT1revealed no statistically significant difference between the symptomatic (n = 16) and asymptomatic BPH (n = 13) groups (Figure 3a). However, we observed that the asymptomatic BPH samples with the largest mass had the highest fold change in IFIT1. Large prostate size is oftentimes associated with LUTS. When we remove the 4 samples that came from asymptomatic BPH patients with a prostate mass greater than 60g, there is a statistically significant 2-fold increase in IFIT1 expression in symptomatic BPH samples (n = 17) when compared to asymptomatic BPH (n = 9) (Figure 3b; p = 0.012, Mann-Whitney).


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. IFIT1 real time PCR with symptomatic and asymptomatic BPH samples. The Mann-Whitney statistical test was utilized for statistical analysis and determined that there was no statistically significant difference between the two groups. b. Real time PCR for IFIT1 in symptomatic BPH and asymptomatic BPH samples in which the prostate mass was less than 60g. Statistical analysis using the Mann-Whitney rank-sum test demonstrates a statistically significant difference between the two groups, p = 0.0118.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: a. IFIT1 real time PCR with symptomatic and asymptomatic BPH samples. The Mann-Whitney statistical test was utilized for statistical analysis and determined that there was no statistically significant difference between the two groups. b. Real time PCR for IFIT1 in symptomatic BPH and asymptomatic BPH samples in which the prostate mass was less than 60g. Statistical analysis using the Mann-Whitney rank-sum test demonstrates a statistically significant difference between the two groups, p = 0.0118.
Mentions: In an attempt to distinguish activation of these genes in response to virus versus other pathogens, we examined the expression profile of interferon-induced tetratricopeptide 1 (IFIT1). IFIT1 expression is activated in response to viruses as well as IFNalpha/beta, which are induced in response to virus. The function of IFIT1 is to inhibit cellular and viral processes such as translation, migration, proliferation, signaling and viral replication.13 Real time PCR for IFIT1revealed no statistically significant difference between the symptomatic (n = 16) and asymptomatic BPH (n = 13) groups (Figure 3a). However, we observed that the asymptomatic BPH samples with the largest mass had the highest fold change in IFIT1. Large prostate size is oftentimes associated with LUTS. When we remove the 4 samples that came from asymptomatic BPH patients with a prostate mass greater than 60g, there is a statistically significant 2-fold increase in IFIT1 expression in symptomatic BPH samples (n = 17) when compared to asymptomatic BPH (n = 9) (Figure 3b; p = 0.012, Mann-Whitney).

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