Metabolomics Analysis Reveals the Differential Metabolites and Establishes the Therapeutic Effect Prediction Nomogram Among CP/CPPS Patients Who Respond or Do Not Respond to LiST

Meng, Jialin; Jin, Chen; Li, Jiawei; Zhang, Song; Zhang, Meng; Hao, Zongyao; Chen, Xianguo; Song, Zhengyao; Zhang, Li; Liang, Chaozhao

doi:10.3389/fimmu.2022.953403

Cited by 3 publications

(1 citation statement)

References 40 publications

(43 reference statements)

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“…Therapeutic mechanisms of LESW include tissue repair, angiogenesis, anti-inflammation, nerve regeneration, and recruitment of stem cells [ 6 , 7 , 8 ]. LESW has been proven to demonstrate therapeutic effects on patients with CP/CPPS [ 9 , 10 ]. However, the mechanism of LESW for the treatment of CP/CPPS remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Low-Energy Shock Wave Suppresses Prostatic Pain and Inflammation by Modulating Mitochondrial Dynamics Regulators on a Carrageenan-Induced Prostatitis Model in Rats

Wang

Lee

et al. 2023

IJMS

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A low-energy shock wave (LESW) has therapeutic effects on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS); however, its mechanism of action remains unclear. We explored the effects of LESW on the prostate and mitochondrial dynamics regulators in a rat model of carrageenan-induced prostatitis. The imbalance of mitochondrial dynamics regulators may affect the inflammatory process and molecules and contribute to CP/CPPS. Male Sprague–Dawley rats received intraprostatic 3% or 5% carrageenan injections. The 5% carrageenan group also received LESW treatment at 24 h, 7 days, and 8 days. Pain behavior was evaluated at baseline, 1 week, and 2 weeks after a saline or carrageenan injection. The bladder and the prostate were harvested for immunohistochemistry and quantitative reverse-transcription polymerase chain reaction analysis. Intraprostatic carrageenan injection induced inflammatory reaction in the prostate and the bladder, decreased the pain threshold, and resulted in the upregulation of Drp-1, MFN-2, NLRP3 (mitochondrial integrity markers), substance P, and CGRP-RCP, whose effects were maintained for 1–2 weeks. LESW treatment suppressed carrageenan-induced prostatic pain, inflammatory reaction, mitochondrial integrity markers, and expression of sensory molecules. These findings support a link between the anti-neuroinflammatory effects of LESW in CP/CPPS and the reversal of cellular perturbations caused by imbalances in mitochondrial dynamics in the prostate.

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Section: Introductionmentioning

confidence: 99%

Low-Energy Shock Wave Suppresses Prostatic Pain and Inflammation by Modulating Mitochondrial Dynamics Regulators on a Carrageenan-Induced Prostatitis Model in Rats

Wang

Lee

et al. 2023

IJMS

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CXCR4 influences PUFA desaturation and oxidative stress injury in experimental prostatitis mice by activating Fads2 via PPARγ

Yi zhang,

Feng,

et al. 2024

Free Radical Biology and Medicine

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The CCL5/CCR5/SHP2 axis sustains Stat1 phosphorylation and activates NF-κB signaling promoting M1 macrophage polarization and exacerbating chronic prostatic inflammation

Jin,

Zhang,

Luo

et al. 2024

Cell Commun Signal

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Background and objective Chronic prostatitis (CP) is a condition markered by persistent prostate inflammation, yet the specific cytokines driving its progression remain largely undefined. This study aims to identify key cytokines involved in CP and investigate their role in driving inflammatory responses through mechanistic and therapeutic exploration. Methods A 48-cytokine panel test was conducted to compare the plasma cytokine profiles between participants with CP-like symptoms (CP-LS) and healthy controls. Experimental autoimmune prostatitis (EAP) models were used for functional validation, with further mechanistic studies performed through in vivo and in vitro assays. Pharmacological inhibition was applied using maraviroc, and pathway inhibitors to assess therapeutic potential. Results Our analysis identified CCL5 as one of the most prominently elevated cytokines in CP-LS patients. Further validation in the EAP model mice confirmed elevated CCL5 levels, highlighting its role in driving prostatic inflammation. Mechanistic studies revealed that CCL5 interacts with the CCR5 receptor, promoting M1 macrophage polarization and activating key inflammatory signaling pathways, including Stat1 and NF-κB, as indicated by increased phosphorylation of Stat1 and p65. In vitro, CCL5 combined with LPS stimulation amplified these effects, further promoting M1 polarization. CCL5 also sustained Stat1 activation by inhibiting its dephosphorylation through reduced interaction with SHP2, leading to prolonged inflammatory signaling. Single-cell transcriptomics confirmed high CCR5 expression in macrophages, correlating with inflammatory pathways. Pharmacological inhibition of CCR5, or its downstream signaling, significantly reduced macrophage-driven inflammation both in vivo and in vitro. Conclusion These findings establish the CCL5/CCR5 axis as a critical driver of persistant prostatic inflammation and present it as a potential therapeutic target for CP. Graphic Abstract The graphic abstract illustrates the central role of the CCL5/CCR5 axis in promoting chronic prostatitis progression. CCL5 binds to the CCR5 receptor on macrophages, enhancing M1 polarization and activating key inflammatory pathways, including Stat1 and NF-κB, as shown by the increased phosphorylation of Stat1 and p65. The interaction also inhibits SHP2-mediated Stat1 dephosphorylation, sustaining prolonged inflammatory signaling. Pharmacological inhibition of CCR5 or its downstream pathways attenuates macrophage-driven inflammation, highlighting this axis as a critical driver and potential therapeutic target for chronic prostatitis. Supplementary Information The online version contains supplementary material available at 10.1186/s12964-024-01943-w.

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Metabolomics Analysis Reveals the Differential Metabolites and Establishes the Therapeutic Effect Prediction Nomogram Among CP/CPPS Patients Who Respond or Do Not Respond to LiST

Cited by 3 publications

References 40 publications

Low-Energy Shock Wave Suppresses Prostatic Pain and Inflammation by Modulating Mitochondrial Dynamics Regulators on a Carrageenan-Induced Prostatitis Model in Rats

Low-Energy Shock Wave Suppresses Prostatic Pain and Inflammation by Modulating Mitochondrial Dynamics Regulators on a Carrageenan-Induced Prostatitis Model in Rats

CXCR4 influences PUFA desaturation and oxidative stress injury in experimental prostatitis mice by activating Fads2 via PPARγ

The CCL5/CCR5/SHP2 axis sustains Stat1 phosphorylation and activates NF-κB signaling promoting M1 macrophage polarization and exacerbating chronic prostatic inflammation

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