MicroRNA‐155 deficiency attenuates inflammation and oxidative stress in experimental autoimmune prostatitis in a TLR4‐dependent manner

Abstract

Abstract 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‐κB) 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‐κB pathway in the prostatic tissues of WT mice with EAP. Furthermore, prostatitis mice had aggravated inflammation scores accompanying the increased interleukin (IL)‐1β, tumor necrosis factor‐α, IL‐6, interferon‐γ, 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‐κB activation, thereby exerting a therapeutic effect in chronic prostatitis treatment.

Keywords

• autoimmune chronic prostatitis
• MicroRNA‐155
• NF‐κB
• TLR4