Melatonin attenuates prostatic inflammation and pelvic pain via Sirt1‐dependent inhibition of the NLRP3 inflammasome in an EAP mouse model
| Autor: | Chang-Sheng Zhan, Yi Liu, Chaozhao Liang, Jing Chen, Li Zhang, Meng Zhang, Hexi Du, Longping Wen, Ligang Zhang, Xianguo Chen |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Inflammasomes Urology Anti-Inflammatory Agents Prostatitis Pharmacology Pelvic Pain Proinflammatory cytokine Melatonin Mice Sirtuin 1 Chronic prostatitis/chronic pelvic pain syndrome Prostate NLR Family Pyrin Domain-Containing 3 Protein medicine Animals Pain Measurement business.industry Pelvic pain Inflammasome medicine.disease Disease Models Animal medicine.anatomical_structure Allodynia Oncology Cytokines medicine.symptom business medicine.drug |
| Zdroj: | The Prostate. 81:1179-1190 |
| ISSN: | 1097-0045 0270-4137 |
| DOI: | 10.1002/pros.24214 |
| Popis: | Background Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common male genitourinary system disease. As a neuroendocrine hormone, melatonin possesses a variety of biological functions, among which its anti-inflammatory effects have recently drawn substantial attention. The purpose of the current research was to study the effect of melatonin on CP/CPPS and the underlying mechanisms using a mouse model of experimental autoimmune prostatitis (EAP). Methods The EAP mouse model was successfully established by subcutaneously injecting a mixture of prostate antigen and complete Freund's adjuvant. On Day 42, hematoxylin-eosin staining was used to evaluate the histological appearance of prostate tissues. Chronic pelvic pain development was assessed by suprapubic allodynia. The levels of inflammation-related cytokines, such as interferon-γ, interleukin (IL)-17, and IL-1β, were detected by enzyme-linked immunosorbent assay. Then, we explored the anti-inflammatory effects of melatonin on CP/CPPS by Western blotting and immunohistochemical staining, by measuring the expression of silent information regulator 1 (Sirt1) and NLRP3 inflammasome-related proteins in EAP mice. Results The EAP model mice exhibited severe diffuse leukocyte infiltration and significantly increased pelvic pain compared to the control mice. In the melatonin treatment group, the histological appearance of the prostate tissues, pelvic pain development, and the levels of proinflammatory cytokines were significantly alleviated compared to the EAP + dimethyl sulfoxide group. Furthermore, we found that the protective effects of melatonin were achieved through activation of the Sirt1 pathway and downregulation of the NLRP3 inflammasome. Conclusions The results indicated that melatonin could attenuate prostate inflammation and pelvic pain by inhibiting the NLRP3 inflammasomes signaling pathway through the activation of Sirt1 in mice with EAP, and these efforts should provide a promising therapeutic strategy for CP/CPPS. |
| Databáze: | OpenAIRE |
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