Basic Research

Exploring mechanism of TLR4/NF⁃κB⁃NLRP3 inflammasome signaling pathway in experimental autoimmune prostatitis rats

  • Liangxi LU ,
  • Hong SHI ,
  • Zhimin HUANG ,
  • Jie LU ,
  • Wenjie. WANG
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  • Department of Andrology,Ren′ai Branch of the First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning 530001,Guangxi,China

Received date: 2024-12-13

  Online published: 2025-03-31

Abstract

Objective The pathogenesis of EAP in rats based on the TLR4/NF-κB?NLRP3 inflammasome signaling pathway was explored. Methods Randomly divide 12 male SD rats into 4 groups using the number table, namely normal group (N), model group (M), Caspase-1 inhibitor group (Caspase-1), and NLRP3 inhibitor MCC950 group (NLRP3), with 3 rats in each group. After drug intervention, relevant indicators were observed by using HE staining, ELISA, WB methods. Results Compared with the N group, the M group rats had showed significant damage in prostate gland structure and infiltration of inflammatory cells. Compared with group N, the expression of TLR4, P?NF-κB P65, NLRP3, ASC, Cleaced?Caspase-1, Cleaced?IL?1β, and IL?18 proteins in the prostate tissue of group M rats had increased(P < 0.01). Compared with group M, the expression of TLR4, P?NF-κB P65, NLRP3, ASC, Cleaced?Caspase-1, Cleaced?IL?1β, and IL?18 proteins in the NLRP3 and Caspase?1 groups had significantly reduced(P < 0.01). The serum levels of IL?1 β, IL?6, IL?8, IL?17A, IL?18, IFN?γ, and TNF?α in group M rats had been significantly higher than those in group N(P < 0.01). But the serum levels of IL?10 had been slightly lower and no statistical significance. The serum levels of IL?1β, IL?6, IL?8, IL?17A, IL?18, IFN?γ, and TNF?α in group M rats had been lower than those in group N(P < 0.01 or P < 0.05), the serum IL?10 level had increased(P < 0.01). Conclusion The activation of TLR4/NF-κB-NLRP3 inflammasome signaling pathway promotes the occurrence and development of prostatitis in EAP rats.

Cite this article

Liangxi LU , Hong SHI , Zhimin HUANG , Jie LU , Wenjie. WANG . Exploring mechanism of TLR4/NF⁃κB⁃NLRP3 inflammasome signaling pathway in experimental autoimmune prostatitis rats[J]. The Journal of Practical Medicine, 2025 , 41(6) : 800 -805 . DOI: 10.3969/j.issn.1006-5725.2025.06.004

References

1 DE WITT-FOY M E, NICKEL J C, SHOSKES D A. Management of chronic prostatitis/chronic pelvic pain syndrome[J]. Eur Urol Focus,2019,5(1):2-4. doi:10.1016/j.euf.2018.08.027
2 中华医学会男科学分会. 慢性前列腺炎/慢性盆腔疼痛综合征诊疗指南[J]. 中华男科学杂志,2022,28(6):544-559.
3 FRANCO J V A, TURK T, JUNG J H, et al. Pharmacological interventions for treating chronic prostatitis/chronic pelvic pain syndrome: A Cochrane systematic review[J]. BJU Int,2020,125(4):490-496. doi:10.1111/bju.14988
4 LIU S J, GAO Q H, DENG Y J, et al. Knowledge domain and emerging trends in chronic prostatitis/chronic pelvic pain syndrome from 1970 to 2020: A scientometric analysis based on VOS viewer and Cite Space[J]. Ann Palliat Med, 2022,11(5):1714-1724. doi:10.21037/apm-21-3068
5 SEOANE P I, LEE B, HOYLE C, et al. The NLRP3-inflammasome as a sensor of organelle dysfunction[J]. J Cell Biol,2020,219(12):e202006194. doi:10.1083/jcb.202006194
6 陆佳伟,刘效谷,张文波. LncRNA及miRNA对NLRP3炎症小体信号的调控机制及其在相关疾病中的意义[J]. 实用医学杂志,2020,36(22):3149-3152.
7 LIU X, CHEN J, YUE S, et al. NLRP3-mediated IL-1β in regulating the imbalance between Th17 and Treg in experimental autoimmune prostatitis[J]. Sci Rep,2024,14(1):18829. doi:10.1038/s41598-024-69512-2
8 MA C G, LIU Y N, WANG H D. NLRP3 inflammasome in expressed prostatic secretions as a potential biomarker of chronic prostatitis/chronic pelvic pain syndrome[J]. Adv Clin Exp Med,2024. doi:10.17219/acem/192548 . Online ahead of print.
9 陆良喜,史宏,黄志敏,等. 前列腺小体miRNA-146a/TLR-4/NF-κB通路在EAP大鼠慢性炎症中的作用及大火草干预的研究[J]. 中国全科医学,2023,26(20):2518-2524.
10 中华中医药学会中药实验药理专业委员会. 慢性前列腺炎动物模型制备规范(草案)[J]. 中国实验方剂学杂志,2018,24(19):10-14.
11 ZHOU Y, WANG J H, HAN J P, et al. Dihydroartemisinin ameliorates chronic nonbacterial prostatitis and epithelial cellular inflammation by blocking the E2F7/HIF1α pathway[J]. Inflamm Res,2022,71:449-460. doi:10.1007/s00011-022-01544-8
12 SEUMEN C H T, GRIMM T M, HAUCK C R. Protein phosphatases in TLR signaling[J]. Cell Commun Signal,2021,19(1):45. doi:10.1186/s12964-021-00722-1
13 ZHU G Q, JEON S H, LEE K W, et al. Electric stimulation hyperthermia relieves inflammation via the suppressor of cytokine signaling 3-toll like receptor 4 pathway in a prostatitis rat model[J]. World J Mens Health,2020,38:359-369. doi:10.5534/wjmh.190078
14 JEON S H, ZhU G Q, KAON E B, et al. Extracorporeal shock wave therapy decreases COX-2 by inhibiting TLR4-NFκB pathway in a prostatitis rat model[J]. Prostate,2019,79:1498-1504. doi:10.1002/pros.23880
15 KIM S, PIAO J J, BANG S, et al. Non-Invasive Radiofrequency Hyperthermia Attenuates HMGB1/TLR4/NF-kappaB Inflammatory Axis in a Chronic Prostatitis/Chronic Pelvic Pain Syndrome Rat Model[J]. World J Mens Health,2024,42(4):855- 864. doi:10.5534/wjmh.230230
16 HUANG Y, XU W, ZHOU R. NLRP3 inflammasome activation and cell death[J]. Cell Mol Immunol,2021,18(9):2114-2127. doi:10.1038/s41423-021-00740-6
17 DONG Y, BONIN J P, DEVANT P, et al.Structural transitions enable interleukin-18 maturation and signaling[J]. Immunity,2024,57(7):1533-1548. doi:10.1016/j.immuni.2024.04.015
18 KELLEY N, JELTEMA D, DUAN Y, et al. The NLRP3 inflammasome: An overview of mechanisms of activation and regulation[J]. Int J Mol Sci,2019,20: 3328. doi:10.3390/ijms20133328
19 FENG R, MENG T, ZHAO X, et al.Isoliquiritigenin reduces experimental autoimmune prostatitis by facilitating Nrf2 activation and suppressing the NLRP3 inflammasome pathway[J]. Mol Immunol,2024,169:37-49. doi:10.1016/j.molimm.2024.03.002
20 LIU S J, GUO B D, GAO Q H, et al. Ursolic acid alleviates chronic prostatitis via regulating NLRP3 inflammasome-mediated Caspase-1/GSDMD pyroptosis pathway[J]. Phytother Res,2024,38(1):82-97. doi:10.1002/ptr.8034
21 CHEN L, LIU Y, YUE S, et al. P2X7R Modulates NEK7-NLRP3 Interaction to Exacerbate Experimental Autoimmune Prostatitis via GSDMD-mediated Prostate Epithelial Cell Pyroptosis[J]. Int J Biol Sci,2024,20(9):3393-3411. doi:10.7150/ijbs.94704
22 ZHANG F, MENG T, FENG R, et al. MIF aggravates experimental autoimmune prostatitis through activation of the NLRP3 inflammasome via the PI3K/AKT pathway[J]. Int Immunopharmacol,2024,141:112891. doi:10.1016/j.intimp.2024.112891
23 HUA X, ZHANG J, CHEN J, et al. Sodium butyrate alleviates experimental autoimmune prostatitis by inhibiting oxidative stress and NLRP3 inflammasome activation via the Nrf2/HO-1 pathway[J]. Prostate,2024,84(7):666-681. doi:10.1002/pros.24683
24 ZHAO X, FENG R, CHEN J, et al. 4-Octyl itaconate alleviates experimental autoimmune prostatitis by inhibiting the NLRP3 inflammasome-induced pyroptosis through activating Nrf2/HO-1 pathway[J]. Prostate,2024,84(4):329-341. doi:10.1002/pros.24652
25 ZHANG J, CHEN J, JIANG Q, et al. Resolvin D1 Attenuates Inflammation and Pelvic Pain Associated with EAP by Inhibiting Oxidative Stress and NLRP3 Inflammasome Activation via the Nrf2/HO-1 Pathway[J]. J Inflamm Res,2023,16: 3365-3379. doi:10.2147/jir.s408111
26 KINRA M, NAMPOOTHIRI M, ARORA D, et al. Reviewing the importance of TLR-NLRP3-pyroptosis pathway and mechanism of experimental NLRP3 inflammasome inhibitors[J]. Scand J Immunol,2022,95(2):e13124. doi:10.1111/sji.13124
27 韩晨阳,张晓玲,杨毅,等. α-突触核蛋白激活NLRP3炎性小体介导神经细胞焦亡的发生[J]. 中国临床药理学与治疗学,2019,24(6):637-643.
28 BAE W J, SHIN D, PIAO J J, et al. Extracorporeal Shockwave Therapy Alleviates Inflammatory Pain by Down-Regulating NLRP3 Inflammasome in Experimental Chronic Prostatitis and Chronic Pelvic Pain Syndrome[J]. World J Mens Health, 2024,42(1):157-167. doi:10.5534/wjmh.220241
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