Urine chemokines indicate pathogenic association of obesity with BPH/LUTS

Tyagi, Pradeep; Motley, Saundra; Kashyap, Mahendra; Pore, Subrata K.; Gingrich, Jeffrey R.; Wang, Zhou; Yoshimura, Naoki; Fowke, Jay H.

doi:10.1007/s11255-015-0992-2

Cited by 10 publications

(9 citation statements)

References 31 publications

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“…This study had only five cases with severe symptoms, but one possible explanation might be that inflammatory chronic prostatitis caused the severe symptoms, leading to lower MCP-1 levels in urine. Tyagi et al studied the association of urinary levels of MCP-1, CXCL-1, CXCL-8, CXCL-10, CCl3 and sIL-1ra with BPH/LUTS and urine levels of CXCL-8, CXCL-10, and sIL-1ra were associated with BPH/LUTS [17]. Tyagi et al used the urine without massage, which might cause the difference from our results.…”

Section: Discussioncontrasting

confidence: 60%

Prostatic Monocyte Chemotactic Protein-1 (MCP-1): A Novel Potential Biomarker for Symptomatic Benign Prostatic Hyperplasia

Fujita¹,

Kellogg²,

Charles³

et al. 2017

MCMR

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Abstract. Monocyte chemotactic protein-1 (MCP-1) is differentially expressed in benign prostatic hyperplasia (BPH) and is a potential clinical biomarker for BPH. We collected urine post-digital rectal examination (DRE) from 48 men who did not have a diagnosis of prostate cancer. We measured MCP-1 levels by enzyme-linked immunosorbent assay (ELISA) and compared them with prostate weight and lower urinary tract symptoms (LUTS) as measured by the International Prostate Symptom Score (I-PSS) utilizing correlation and regression analyses. In post-DRE urine, higher MCP-1 levels were associated with increased I-PSS but not with prostate volume. MCP-1 levels in men with prostate enlargement were significantly higher than those in men without enlargement. In multivariable regression adjusting for age, prostate volume, and PSA,higher urinary MCP-1 was associated with significantly higher I-PSS. Since MCP-1 is preferentially expressed in BPH tissue, these data suggest that MCP-1 may be a novel biomarker for clinically significant BPH.Keywords: MCP-1, LUTS, urine marker, benign prostatic hyperplasia IntroductionBenign prostate hyperplasia (BPH) is a common disease affecting older men caused by unregulated prostatic stromal and epithelial growth resulting in prostate enlargement, bladder outlet obstruction, and lower urinary tract symptoms (LUTS) [1]. Despite intensive researches over the last several decades, the molecular mechanisms underlying prostatic enlargement and symptomatic bladder outlet obstruction remain obscure, and specific clinical markers for symptomatic BPH have yet to be developed. We previously used a human cytokine array to search for cytokines in expressed prostatic secretions (EPS) from radical prostatectomy specimens that may be associated with prostate enlargement, and found that monocyte/macrophage chemoattractant protein-1 (MCP-1, CCL2) in EPS was associated with prostate size [2]. MCP-1 is a member of the CC chemokine superfamily and plays a critical role in the recruitment and activation of monocytes during inflammation [3]. MCP-1 is secreted from prostatic stromal cells and stimulates the proliferation of prostatic epithelial cells in vitro. Immunohistochemical studies indicated that MCP-1 was upregulated in benign prostatic hyperplasia (BPH) lesions, and MCP-1 levels in EPS correlated with mRNA levels of the macrophage marker CD68 [4]. Based on these data, we hypothesize that MCP-1 levels in urine after DRE, which is enriched in prostatic contents, could serve as a specific clinical marker for symptomatic BPH. Therefore, we evaluated associations of MCP-1 levels in urine collected after DRE with prostate volume and LUTS by enzyme-linked immunosorbent assay (ELISA).

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Section: Discussioncontrasting

confidence: 60%

Prostatic Monocyte Chemotactic Protein-1 (MCP-1): A Novel Potential Biomarker for Symptomatic Benign Prostatic Hyperplasia

Fujita¹,

Kellogg²,

Charles³

et al. 2017

MCMR

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“…Besides, median urine levels of sIL‐1Ra measured here in overweight or obese men with BPH were comparable to the published levels of sIL‐1Ra in serum of lean men, which lend support to the suggestion that serum elevation of sIL‐1Ra precedes the elevation in urine. The larger sample size of this study was able to reproduce the association of sIL‐1Ra in urine with obesity measures of BMI, waist circumference and waist‐hip ratio, found earlier in a pilot study . Therefore, sIL‐1Ra is the key molecular correlate for the obesity or greater body size of BPH patients, which is detectable in both serum and urine.…”

Section: Discussionmentioning

confidence: 57%

“…The larger sample size of this study was able to reproduce the association of sIL-1Ra in urine with obesity measures of BMI, waist circumference and waist-hip ratio, found earlier in a pilot study. 19 Therefore, sIL-1Ra is the key molecular correlate for the obesity or greater body size of BPH patients 23,24 , which is detectable in both serum and urine. are chemotactic for the infiltration of CD3 + T lymphocytes and CD20 B lymphocytes, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…The present study seeks to evaluate whether urinary chemokines can reflect the clinical attributes of BPH/LUTS patients. The selection of the chemokines for the present study was based on the known role of following chemokines CXCL‐1, CXCL‐8, CXCL‐10, CCL2, CCL3, and CCL5 in the chemoattraction of CD3+ and CD20+ lymphocytes and the reports on detection of other included proteins in the prostate tissue or biofluids of BPH patients or patients suffering from LUTS …”

Section: Introductionmentioning

confidence: 99%

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Molecular correlates in urine for the obesity and prostatic inflammation of BPH/LUTS patients

et al. 2017

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Purpose: Benign prostatic hyperplasia (BPH) is strongly associated with obesity and prostatic tissue inflammation, but the molecular underpinning of this relationship is not known. Here, we examined the association between urine levels of chemokines/ adipokines with histological markers of prostate inflammation, obesity, and lower urinary tract symptoms LUTS in BPH patients. Methods: Frozen urine specimens from 207 BPH/LUTS patients enrolled in NashvilleMen's Health Study were sent for blinded analysis of 11 analytes, namely sIL-1RA, CXC chemokines (CXCL-1, CXCL-8, CXCL-10), CC chemokines (CCL2, CCL3, CCL5), PDGF-BB, interleukins IL-6, IL-17, and sCD40L using Luminex™ xMAP® technology.After adjusting for age and medication use, the urine levels of analytes were correlated with the scales of obesity, prostate inflammation grade, extent, and markers of lymphocytic infiltration (CD3 and CD20) using linear regression.Results: sIL-1RA levels were significantly raised with higher BMI, waist circumference and waist-hip ratio in BPH patients after correction for multiple testing (P = 0.02). Men with greater overall extent of inflammatory infiltrates and maximal CD3 infiltration were marginally associated with CXCL-10 (P = 0.054) and CCL5 (P = 0.054), respectively. CCL3 in 15 patients with moderate to severe grade inflammation was marginally associated with maximal CD20 infiltration (P = 0.09), whereas CCL3 was undetectable in men with mild prostate tissue inflammation.There was marginal association of sCD40L with AUA-SI scores (P = 0.07).Conclusions: Strong association of sIL-1RA in urine with greater body size supports it as a major molecular correlate of obesity in the urine of BPH patients. Increased urine levels of CXCL-10, CCL5, and CCL3 were marginally associated with the scores for prostate tissue inflammation and lymphocytic infiltration. Overall, elevated urinary chemokines support that BPH is a metabolic disorder and suggest a molecular link between BPH/LUTS and prostatic inflammation. K E Y W O R D S BPH, inflammation, obesity, urineThe Prostate. 2018;78:17-24.wileyonlinelibrary.com/journal/pros

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“…The levels of these cytokines (e.g., CXCL-8, CXCL-10, and sIL-1ra) were increased in BPH/LUTS patients, suggesting a significant association between obesity, inflammation, and BPH/LUTS. 6 …”

Section: Metabolism Metabolic Syndrome and Prostate Healthmentioning

confidence: 99%

Looking to the metabolic landscapes for prostate health monitoring

Kim

2017

Prostate International

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Abnormal metabolism is a widely accepted biological signature of prostatic diseases, including prostate cancer and benign prostate hyperplasia. Recently accumulated epidemiological and experimental evidence illustrate that the metabolic syndrome, impaired mitochondrial function, and prostatic pathological conditions intersect. The perturbed metabolism and metabolic mediates influence key signaling pathways in various prostatic pathological conditions. This short review article aids to highlight recent findings on metabolism, metabolic mechanisms, and mitochondrial metabolism as a possible route to finding a cure for prostate diseases, including prostate cancer. The effort to better understand the role that mitochondria plays in cancer metabolism and the biological meaning of defective and/or deleted mitochondrial DNA in cancer will also be discussed.

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Urine chemokines indicate pathogenic association of obesity with BPH/LUTS

Cited by 10 publications

References 31 publications

Prostatic Monocyte Chemotactic Protein-1 (MCP-1): A Novel Potential Biomarker for Symptomatic Benign Prostatic Hyperplasia

Prostatic Monocyte Chemotactic Protein-1 (MCP-1): A Novel Potential Biomarker for Symptomatic Benign Prostatic Hyperplasia

Molecular correlates in urine for the obesity and prostatic inflammation of BPH/LUTS patients

Looking to the metabolic landscapes for prostate health monitoring

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