MicroRNA-155 deficiency attenuates inflammation and oxidative stress in experimental autoimmune prostatitis in a TLR4-dependent manner
MicroRNA-155 deficiency attenuates inflammation and oxidative stress in experimental autoimmune prostatitis in a TLR4-dependent manner
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DOI：
10.1002/kjm2.12229
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发表时间：
2020-05-21
影响因子：
3.3
通讯作者：
Wang, Xu-Liang
中科院分区：
文献类型：
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作者：
Fu, Xian;He, Hua-Dong;Wang, Xu-Liang
目的探讨microRNA-155（miR-155）缺陷对实验性自身免疫性前列腺炎（EAP）的保护作用机制。将野生型（WT）和miR-155（-/-）小鼠注射完全弗氏佐剂和前列腺抗原以建立EAP模型后，随机选择一半注射脂多糖（LPS，一种TLR 4配体）。然后进行以下实验：von Frey细丝、苏木精-伊红（HE）染色、真实的实时定量聚合酶链反应（qRT-PCR）、蛋白质印迹和酶联免疫吸附测定（ELISA）。用相应试剂盒检测超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）活性及丙二醛（MDA）含量。与前列腺炎WT小鼠相比，前列腺炎miR-155（-/-）小鼠表现出减弱的盆腔触觉异常性疼痛/痛觉过敏和抑制的TLR 4/核因子-κ B（NF-κ B）通路。此外，LPS增强了EAP WT小鼠前列腺组织中miR-155的上调和TLR 4/NF-κ B通路的激活。此外，前列腺炎小鼠的炎症评分加重，伴随着前列腺组织中白细胞介素（IL）-1 β、肿瘤坏死因子-α、IL-6、干扰素-γ、IL-12和MDA的增加，而IL-10、SOD和GSH-Px降低，IL-4不变。与WT + EAP组和miR-155（-/-）+ EAP + LPS组的小鼠相比，miR-155（-/-）+ EAP组的小鼠具有降低的炎症和氧化应激。miR-155缺陷改善了EAP小鼠的盆腔触觉异常性疼痛/痛觉过敏，并以涉及NF-κ B活化的TLR 4依赖性方式改善了前列腺组织中的炎症和氧化应激，从而在慢性前列腺炎治疗中发挥了治疗效果。
To explore the mechanism of microRNA-155 (miR-155) deficiency, protecting against experimental autoimmune prostatitis (EAP) in a toll-like receptor 4 (TLR4)-dependent manner. After wild-type (WT) and miR-155(-/-) mice were injected with complete Freund's adjuvant and prostate antigen to establish EAP model, half were randomly selected for injection with lipopolysaccharide (LPS, a TLR4 ligand). The following experiments were then performed: von Frey filaments, hematoxylin-eosin (HE) staining, real time quantitative polymerase chain reaction (qRT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA). And the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and the level of Malondialdehyde (MDA) were detected by corresponding kits. miR-155(-/-) mice with prostatitis exhibited the attenuated pelvic tactile allodynia/hyperalgesia and the suppressed TLR4/nuclear factor-kappa B (NF-kappa B) pathway as compared with the WT mice with prostatitis. In addition, LPS enhanced the upregulation of miR-155 and the activation of the TLR4/NF-kappa B pathway in the prostatic tissues of WT mice with EAP. Furthermore, prostatitis mice had aggravated inflammation scores accompanying the increased interleukin (IL)-1 beta, tumor necrosis factor-alpha, IL-6, interferon-gamma, IL-12, and MDA in prostatic tissues with the decreased IL-10, SOD and GSH-Px, and the unaltered IL-4. Compared with the mice from the WT + EAP group and the miR-155(-/-) + EAP + LPS group, mice from the miR-155(-/-) + EAP group had decreased inflammation and oxidative stress. miR-155 deficiency ameliorated pelvic tactile allodynia/hyperalgesia in EAP mice and improved inflammation and oxidative stress in prostatic tissues in a TLR4-dependent manner involving NF-kappa B activation, thereby exerting a therapeutic effect in chronic prostatitis treatment.