A Novel Insight into the Immune-Related Interaction of Inflammatory Cytokines in Benign Prostatic Hyperplasia

Naiyila, Xiaokaiti; Li, Jinze; Huang, Yin; Chen, Bo; Zhu, Mengli; Li, Jin; Chen, Zeyu; Yang, Lu; Ai, Jianzhong; Wei, Qiang; Liu, Liangren; Cao, Deliang

doi:10.3390/jcm12051821

Cited by 9 publications

(7 citation statements)

References 107 publications

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Section: Discussionmentioning

confidence: 99%

“…21 Notably, oxidative stress can trigger inflammation and prompt prostatic stromal cells to secrete cytokines and growth factors, which, in turn, stimulate the growth of prostatic epithelial cells and enhance extracellular matrix deposition. 22 Additionally, oxidative stress can drive cellular senescence, characterized by altered gene expression and definite growth arrest, leading to cellular aging and dysfunction. Senescent cells release pro-inflammatory and pro-fibrotic factors that further impede prostate function by promoting enlargement and fibrosis.…”

Section: Discussionmentioning

confidence: 99%

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Leptin Mediates Prostate Stromal Cell Proliferation, Smooth Muscle Contraction, and Mitochondrial Function in Benign Prostate Hyperplasia

Wang,

Guo,

Liu

et al. 2023

DMSO

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Introduction Leptin is a metabolic peptide hormone produced by adipocytes, with proven roles in proliferation of prostate cancer cells and of prostate cells in animal models of benign prostatic hyperplasia (BPH). Thus, the role of leptin as a molecular link connecting BPH and lower urinary tract symptoms (LUTS) suggestive of BPH with metabolic symptoms appears feasible but is still unknown. In fact, a connection between metabolic syndrome and BPH is becoming increasingly evident from epidemiologic studies. Key factors of Lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH/LUTS) are increased prostate smooth muscle tone, and prostate enlargement. Here, we examined the effects of leptin on contraction of human prostate smooth muscle and on growth of stromal cells. Methods We performed microarray analysis to identify genes (fold change ≥ 1.5) associated with BPH/LUTS progression, such as those involved in proliferation, apoptosis, and mitochondrial metabolism, in rat prostate tissue (data from GSE129561). We then used electric field stimulation (EFS) to induce frequency-dependent, neurogenic contractions of human prostate strips, which were enhanced by leptin. We also examined the effect of leptin on human prostate stromal cells (WPMY-1) and found increased cell proliferation and viability upon exposure. To explore the underlying mechanism, we conducted mitochondrial stress assay using near-infrared (NIR) fluorescent dye and flow cytometry (FACS) analysis and observed reduced cellular apoptosis and preserved mitochondrial membrane potential (∆ψM) after leptin treatment. Results Microarray analysis reveals that leptin regulates prostate smooth muscle contraction and stromal cell proliferation, shedding new light on its involvement in BPH/LUTS pathogenesis and mitochondrial function. We found that leptin enhanced the proliferation rate of prostate stromal cells relative to the control group (0.67 ± 0.05 vs 0.54 ± 0.08, p-value= 0.024). Moreover, leptin (100 ng/mL) potentiated the frequency-dependent, neurogenic contractions of prostate strips elicited by EFS (p= 0.047 between leptin and control group). We also show that leptin treatment increased the mitochondrial membrane potential of prostate stromal cells and inhibited mitochondrial apoptosis. Discussion Our results indicate that leptin stimulates the contractility and proliferation of smooth muscle and stromal cells in the human prostate, implying a potential role for leptin in exacerbating BPH/LUTS in obese men. Leptin modulation may be a beneficial therapeutic strategy for patients with metabolic syndrome and BPH/LUTS. Further studies are warranted to elucidate the mechanisms and implications of the leptin system in BPH/LUTS.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Leptin Mediates Prostate Stromal Cell Proliferation, Smooth Muscle Contraction, and Mitochondrial Function in Benign Prostate Hyperplasia

Wang,

Guo,

Liu

et al. 2023

DMSO

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“…All these events determine stromal proliferation, transdifferentiation, and extracellular matrix production. The proinflammatory and profibrotic microenvironment causes a local vicious cycle, which can lead to the overproliferation of BPH nodules and concomitantly create a suitable microenvironment for cancer growth and progression [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

The Effects of Caloric Restriction on Inflammatory Targets in the Prostates of Aged Rats

Rago,

Conforti,

La Russa

et al. 2024

IJMS

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Numerous animal models have demonstrated that caloric restriction (CR) is an excellent tool to delay aging and increase the quality of life, likely because it counteracts age-induced oxidative stress and inflammation. The aging process can affect the prostate in three ways: the onset of benign prostatic hyperplasia, prostatitis, and prostate cancer. In this study, we used 14 aged male Sprague Dawley rats, which were allocated into two groups, at the age of 18 months old. One group was fed ad libitum (a normal diet (ND)), and the other group followed a caloric restriction diet with a 60% decrease in intake. The rats were sacrificed at the age of 24 months. By immunohistochemical (IHC) and Western blot (WB) analyses, we studied the variations between the two groups in immune inflammation and fibrosis-related markers in aged prostate tissues. Morphological examinations showed lower levels of prostatic hyperplasia and fibrosis in the CR rats vs. the ND rats. The IHC results revealed that the prostates of the CR rats exhibited a lower immune proinflammatory infiltrate level and a reduced expression of the NLRP3 inflammasome pathway, together with significantly reduced expressions of mesenchymal markers and the profibrotic factor TGFβ1. Finally, by WB analysis, we observed a reduced expression of ERα, which is notoriously implicated in prostate stromal proliferation, and increased expressions of SOD1 and Hsp70, both exerting protective effects against oxidative stress. Overall, these data suggest that CR brings potential benefits to prostatic tissues as it reduces the physiological immune–inflammatory processes and the tissue remodeling caused by aging.

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“…In line with chronic inflammation, BPH tissue exhibits a fundamental re-landscaping of immune infiltrates similar to PCa, showing a higher density of immune cells (mostly T cells) than healthy prostates [ 11 , 12 ]. The pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNFα), interleukin-6 (IL-6), and interleukin-8 (IL-8), are elevated in the serum and prostate tissue of BPH patients [ 13 , 14 ]. Understanding the interplay between the immune system and the prostate gland is essential for the development of new diagnostic and therapeutic approaches.…”

Section: Introductionmentioning

confidence: 99%

Phenotype and Reactivity of Lymphocytes Expanded from Benign Prostate Hyperplasic Tissues and Prostate Cancer

Ahmed

Lozano

Anastasio

et al. 2023

Cancers

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Benign prostate hyperplasia (BPH) is a frequent condition in aging men, which affects life quality, causing principally lower urinary tract symptoms. Epidemiologic studies suggest that BPH may raise the risk of developing prostate cancer (PCa), most likely promoting a chronic inflammatory environment. Studies aiming at elucidating the link and risk factors that connect BPH and PCa are urgently needed to develop prevention strategies. The BPH microenvironment, similar to the PCa one, increases immune infiltration of the prostate, but, in contrast to PCa, immunosuppression may not be established yet. In this study, we found that prostate-infiltrating lymphocytes (PILs) expanded from hyperplastic prostate tissue recognized tumor-associated antigens (TAA) and autologous tissue, regardless of the presence of tumor cells. PILs expanded from BPH samples of patients with PCa, however, seem to respond more strongly to autologous tissue. Phenotypic characterization of the infiltrating PILs revealed a trend towards better expanding CD4+ T cells in infiltrates derived from PCa, but no significant differences were found. These findings suggest that T cell tolerance is compromised in BPH-affected prostates, likely due to qualitative or quantitative alterations of the antigenic landscape. Our data support the hypothesis that BPH increases the risk of PCa and may pave the way for new personalized preventive vaccine strategies for these patients.

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A Novel Insight into the Immune-Related Interaction of Inflammatory Cytokines in Benign Prostatic Hyperplasia

Cited by 9 publications

References 107 publications

Leptin Mediates Prostate Stromal Cell Proliferation, Smooth Muscle Contraction, and Mitochondrial Function in Benign Prostate Hyperplasia

Leptin Mediates Prostate Stromal Cell Proliferation, Smooth Muscle Contraction, and Mitochondrial Function in Benign Prostate Hyperplasia

The Effects of Caloric Restriction on Inflammatory Targets in the Prostates of Aged Rats

Phenotype and Reactivity of Lymphocytes Expanded from Benign Prostate Hyperplasic Tissues and Prostate Cancer

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