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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. CFI real time PCR results for symptomatic BPH compared to asymptomatic BPH. The student’s t test was utilized in the statistical analysis and resulted in a statistically significant p value of 0.0012. b. Real time PCR for OAS2 gene expression in symptomatic and asymptomatic BPH. Statistical analysis was performed using the Mann-Whitney test, which resulted in a statistically significant difference between the two groups, p = 0.0043.
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Figure 1: a. CFI real time PCR results for symptomatic BPH compared to asymptomatic BPH. The student’s t test was utilized in the statistical analysis and resulted in a statistically significant p value of 0.0012. b. Real time PCR for OAS2 gene expression in symptomatic and asymptomatic BPH. Statistical analysis was performed using the Mann-Whitney test, which resulted in a statistically significant difference between the two groups, p = 0.0043.

Mentions: Relative complement factor I (CFI) mRNA expression was determined by real time PCR analysis using symptomatic BPH (n = 17)or asymptomatic BPH samples (n = 9). The patients with asymptomatic BPH reported AUA scores of less than or equal to 12. Specifications regarding patient samples can be found in Supplemental Table 1. CFI inactivates C3b and C4b; two key players in the innate immune systems complement pathway activation.9 Analysis of the CFI real time PCR data using the BPH1 cell line as a calibrator and GAPDH as a reference gene reveals that the symptomatic BPH samples exhibit a 5-fold increase in CFI expression compared to the asymptomatic BPH samples (Figure 1a; p = 0.0012, t-test).


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. CFI real time PCR results for symptomatic BPH compared to asymptomatic BPH. The student’s t test was utilized in the statistical analysis and resulted in a statistically significant p value of 0.0012. b. Real time PCR for OAS2 gene expression in symptomatic and asymptomatic BPH. Statistical analysis was performed using the Mann-Whitney test, which resulted in a statistically significant difference between the two groups, p = 0.0043.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: a. CFI real time PCR results for symptomatic BPH compared to asymptomatic BPH. The student’s t test was utilized in the statistical analysis and resulted in a statistically significant p value of 0.0012. b. Real time PCR for OAS2 gene expression in symptomatic and asymptomatic BPH. Statistical analysis was performed using the Mann-Whitney test, which resulted in a statistically significant difference between the two groups, p = 0.0043.
Mentions: Relative complement factor I (CFI) mRNA expression was determined by real time PCR analysis using symptomatic BPH (n = 17)or asymptomatic BPH samples (n = 9). The patients with asymptomatic BPH reported AUA scores of less than or equal to 12. Specifications regarding patient samples can be found in Supplemental Table 1. CFI inactivates C3b and C4b; two key players in the innate immune systems complement pathway activation.9 Analysis of the CFI real time PCR data using the BPH1 cell line as a calibrator and GAPDH as a reference gene reveals that the symptomatic BPH samples exhibit a 5-fold increase in CFI expression compared to the asymptomatic BPH samples (Figure 1a; p = 0.0012, t-test).

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