The role of inflammatory cytokines and ERK1/2 signaling in chronic prostatitis/chronic pelvic pain syndrome with related mental health disorders

Hu, Chao; Yang, Hualan; Zhao, Ying; Chen, Xiang; Dong, Youhai; Li, Long; Dong, Yuefu; Cui, Jiefeng; Zhu, Tongyu; Zheng, Ping; Lin, Chen; Dai, Jingbo

doi:10.1038/srep28608

Cited by 38 publications

(42 citation statements)

References 56 publications

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“…Quick et al had established the CP/CPPS rat model and found that MCP‐1 and MIP‐1a were up‐regulated in prostatic fluid, in addition, they also confirmed that these two chemokines were associated with chronic pain. On the other hand, IL‐1β and TNF‐α were the vital proinflammatory factors, which are confirmed in numerous studies to greatly affect the development of CP/CPPS . IL‐6 is a major immune factor in inflammatory response, which regulates IL‐2 production and down‐regulates the synthesis of IL‐1β and TNF‐a.…”

Section: Discussionmentioning

confidence: 85%

Lycopene attenuates chronic prostatitis/chronic pelvic pain syndrome by inhibiting oxidative stress and inflammation via the interaction of NF‐κB, MAPKs, and Nrf2 signaling pathways in rats

et al. 2020

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Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is identified as a urinary andrological diseases that afflict men due to various discomforts. It is urgent and meaningful to develop the novel and effective treatments as a result of the unclear etiology and dismal therapeutic effect of CP/CPPS. Lycopene exerts a crucial role in numerous chronic inflammatory diseases owing to its potent antioxidant capacity.Objective: This study aimed to observe the effect of lycopene on CP/CPPS and to explore the underlying mechanisms. Materials and Methods:A CP/CPPS model with complete Freund's adjuvant was established in this study. Afterward, intragastric lycopene or corn oil was administered daily for 4 consecutive weeks. Finally, the cardiac blood and prostate tissue samples were collected from rats to carry out related evaluation and testing. Results:It was found in this study that lycopene alleviated changes in prostate histopathology compared with those in the complete Freund's adjuvant-induced CP/ CPPS model rats without lycopene treatment. Furthermore, lycopene was suggested to reduce the levels of chemokines MCP1 and MIP-1α, down-regulate the expression levels of cytokines (such as TNFα, IL-1β, IL-2, and IL-6), and up-regulate those of CAT, GSH-PX, and T-SOD, decrease that of malondialdehyde. Moreover, it also inhibited the phosphorylation of MAPKs, NF-κB, and enhanced phosphorylation of the Nrf2 in the CP/CPPS rat model. Discussion and Conclusions:The findings in this study suggest that lycopene exerts potent anti-CP/CPPS effects through alleviating inflammatory response and oxidative stress, which is probably attributed to the interaction of NF-κB, MAPKs, and Nrf2 signaling pathways in rats. As a natural antioxidant, lycopene may serve as a promising pharmaceutical preparation for treating CP/CPPS.

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Section: Discussionmentioning

confidence: 85%

Lycopene attenuates chronic prostatitis/chronic pelvic pain syndrome by inhibiting oxidative stress and inflammation via the interaction of NF‐κB, MAPKs, and Nrf2 signaling pathways in rats

et al. 2020

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“…Inflammatory and autoimmune mechanism may play an important role in the development of cp/cpps. Several cytokines, including IL‐1α, IL‐1β, IL‐4, IL‐13 and TNF‐α, have been found apparently higher than control group both in the serum of CP/CPPS patients and CP/CPPS rat prostates(Hu et al., ). Inflammatory cells, such as T lymphocytes, B lymphocytes and macrophages, were detected in the prostatic massage fluid of cp/cpps patients in the absence of infections (Ludwig et al., ).These evidence indicate an ongoing autoimmune process and inflammation within the prostate.…”

Section: Introductionmentioning

confidence: 99%

Establishment of experimental autoimmune prostatitis model by T₂peptide in aluminium hydroxide adjuvant

et al. 2017

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A mouse model was developed to simulate the clinical features of chronic prostatitis/chronic pelvic pain syndrome using peptide (T ). Forty C57BL/6 mice were divided into four groups of 10 mice each, averagely and randomly. T plus aluminium hydroxide adjuvant group was given subcutaneous injection with the emulsion mixture of T and aluminium hydroxide adjuvant, the T group with T , the aluminium hydroxide adjuvant group with aluminium hydroxide adjuvant and the normal control group with 0.9/% NaCl solution. Haematoxylin andeosin staining was used to observe the inflammation of the prostate. Plasma levels of TNF-α and CRP were detected by ELISA kit. The expression of IL-1βin the prostate was investigated by immunohistochemistry. The statistical differences between the groups were compared by t test. Histopathological analyses demonstrated that prostate lesions were most severe in the group immunised with T plus aluminium hydroxide adjuvant. Plasma levels of TNF-α and CRP were statistically elevated compared with control groups. The expression levels of IL-1β in the prostate were more obvious than control groups. T in aluminium hydroxide adjuvant subcutaneous injection could successfully set up experimental autoimmune prostatitis in C57BL/6 mice. This murine model would be greatly beneficial to further comprehend the aetiology, pathogenesis and explicit treatment of CP/CPPS.

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“…Only in recent years, a few studies have examined the emotional effects of prostatitis in animal models. Hu et al 9 reported that EAP was closely associated with depressive‐like behavior, which was assessed by OFT. Consistent with this result, in this study, the exploratory behaviors in the OFT were more significantly reduced in the EAP group than that in the control group.…”

Section: Discussionmentioning

confidence: 99%

“…Some researchers have advocated for the participation of hypothalamic‐pituitary‐adrenal axis dysfunction, pain, and personality changes in the CP/CPPS‐related mental disorders 7,8 . Also, prostate‐derived inflammatory cytokines that cross the blood‐brain barrier and further activate ERK1/2 signaling in several brain areas have been linked to the psychiatric symptoms in CP/CPPS 9 . However, up to date, the exact mechanisms underlying the association between CP/CPPS and depression are still unclear.…”

Section: Introductionmentioning

confidence: 99%

Abnormal gut microbiota composition is associated with experimental autoimmune prostatitis‐induced depressive‐like behaviors in mice

Liu

Zhang

et al. 2020

The Prostate

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Background: Depressive symptoms are found in approximately 78% of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) patients, but the pathological mechanisms remain unknown. Increasing evidence suggests that abnormal gut microbiota may play an important role in depression. Thus, we aimed to investigate whether gut microbiota contributes to CP/CPPS-associated depression by using a mouse model of experimental autoimmune prostatitis (EAP).Methods: Male nonobese diabetic mice were immunized twice by subcutaneous injection of prostate antigen and adjuvant. Behavioral tests consisted of an open field test, sucrose preference test, forced swimming tests, and tail suspension test was used to confirm the depression-like symptoms that were induced by EAP. Then, fecal samples were collected, and 16S ribosomal RNA gene sequencing was performed to detect differences in gut microbiota composition between control and EAP group. Additionally, fecal bacteria from the control and EAP mice were transplanted into antibiotics-induced pseudo-germ-free mice to investigate the effects on host behaviors and the composition of gut bacteria.Results: EAP was successfully established and exhibited depressive-like behaviors in mice. The 16S rRNA analysis of fecal samples indicated the abnormal composition of gut microbiota in the EAP mice compared to the control mice. In the fecal microbiota transplant study, antibiotics-treated pseudo-germ-free mice presented depressive states as compared to naïve mice. Fecal bacteria transplant from EAP mice, but not from control mice, into the pseudo-germ-free mice, significantly exaggerated host depression-like behaviors. Moreover, fecal bacteria transplants from control and EAP mice induced distinct alterations in α-diversity and β-diversity indices. In all, 24 bacteria at six phylogenetic levels were remarkably changed by the fecal bacteria transplantation.Conclusions: Abnormal gut microbiota composition after EAP induction may contribute to the development of depression in mice. A therapeutic strategy that targets gut microbiota may provide an alternative treatment for alleviating this condition. K E Y W O R D Sdepression, fecal bacteria transplantation, gut microbiota, prostatitis

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The role of inflammatory cytokines and ERK1/2 signaling in chronic prostatitis/chronic pelvic pain syndrome with related mental health disorders

Cited by 38 publications

References 56 publications

Lycopene attenuates chronic prostatitis/chronic pelvic pain syndrome by inhibiting oxidative stress and inflammation via the interaction of NF‐κB, MAPKs, and Nrf2 signaling pathways in rats

Lycopene attenuates chronic prostatitis/chronic pelvic pain syndrome by inhibiting oxidative stress and inflammation via the interaction of NF‐κB, MAPKs, and Nrf2 signaling pathways in rats

Establishment of experimental autoimmune prostatitis model by T₂peptide in aluminium hydroxide adjuvant

Abnormal gut microbiota composition is associated with experimental autoimmune prostatitis‐induced depressive‐like behaviors in mice

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The role of inflammatory cytokines and ERK1/2 signaling in chronic prostatitis/chronic pelvic pain syndrome with related mental health disorders

Cited by 38 publications

References 56 publications

Lycopene attenuates chronic prostatitis/chronic pelvic pain syndrome by inhibiting oxidative stress and inflammation via the interaction of NF‐κB, MAPKs, and Nrf2 signaling pathways in rats

Lycopene attenuates chronic prostatitis/chronic pelvic pain syndrome by inhibiting oxidative stress and inflammation via the interaction of NF‐κB, MAPKs, and Nrf2 signaling pathways in rats

Establishment of experimental autoimmune prostatitis model by T2peptide in aluminium hydroxide adjuvant

Abnormal gut microbiota composition is associated with experimental autoimmune prostatitis‐induced depressive‐like behaviors in mice

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Establishment of experimental autoimmune prostatitis model by T₂peptide in aluminium hydroxide adjuvant