Tissue Kallikrein Protects Rat Prostate against the Inflammatory Damage in a Chronic Autoimmune Prostatitis Model via Restoring Endothelial Function in a Bradykinin Receptor B2-Dependent Way

Abstract

Objective. The aim of this study was to investigate whether tissue kallikrein (KLK1) can protect the prostate from inflammatory damage and the mechanism involved in it. Methods. A total of 50 male Wistar rats were used in this study. Initially, 20 rats were sacrificed to obtain the prostate antigen to induce experimental autoimmune prostatitis (EAP), and the remaining 30 rats were randomly divided into 5 experimental groups (normal control group (NC group), NC+KLK1 group (NCK group), EAP group, EAP+KLK1 group (EAPK group), and EAP+KLK1+HOE140 group (EAPKH group); n = 6 ). It should be explained that KLK1 mainly exerts its biological effects through bradykinin, and HOE140 is a potent and selective bradykinin receptor B2 (BDKRB2) antagonist. EAP was induced by intradermal injection of 15 mg/ml prostate antigen and complete Freund’s adjuvant on days 0, 14, and 28. KLK1 was injected via tail vein at a dose of 1.5 × 10 − 3 PAN U/kg once a day, and HOE140 was administered by intraperitoneal injection at 20 μg/kg once every two days. Rats were sacrificed on day 42. The RNA and protein of the rat prostate were extracted to analyze the expression differences of KLK1, as well as the inflammation-, fibrosis-, and oxidative stress-related genes. The inflammatory cell infiltration and microvessel density of the prostate were also analyzed by pathological examination. In addition, pathological analysis was performed on prostate samples from patients undergoing benign prostate hyperplasia (BPH) surgery. Results. The expression of KLK1 in the prostate decreased in the EAP group as well as BPH patients with obvious inflammation. KLK1 administration significantly inhibited inflammatory cell infiltration and reduced the production of inflammatory cytokines in the EAPK group. Prostate samples from the EAP group showed increased infiltration of T cells and macrophages, as well as gland atrophy, hypoxia, fibrosis, and angiogenesis. KLK1 administration upregulated endothelial nitric oxide synthase (eNOS) expression and suppressed oxidative stress, as well as transforming growth factor β1 (TGF-β) signaling pathways and the proangiogenic vascular endothelial growth factor (VEGF) in the EAPK group. However, in the EAPKH group in which HOE140 blocked BDKRB2, the beneficial effects of KLK1 were all cancelled. In addition, KLK1 intervention in normal rats had no obvious side effects. Conclusion. The KLK1 expression is inhibited in the inflamed prostates of humans and rats. Exogenous KLK1 restored endothelial function via a BDKRB2-dependent way and then played a role in improving microcirculation and exerted anti-inflammatory, antifibrotic, and antioxidative stress effects in the rat chronic-inflamed prostate.

Evaluation the level of human kallikrein-2-hk2, prostate specific antigen and some biochemical parameters in sera of patients with prostate disease

“…Nakamura (37) et al who indicated to the About 54% of BPH patients avoided biopsy based on PSA/hk2 results. Studies did not refer to the evaluation of the level of hk2 in patients with prostatitis, but that Zhang (39) et al In an experimental study, they indicated that the level of kallikrein is lower in mice with prostatitis compared to mice with BPH. As for the FGG level, Table (1) shows that the mean ± standard deviation of the FGG level was (2138.21 ± 283.629) ng/ml in patients of the G1 group and (1277.084 ± 259.377)ng/ml in patients in the G2 group and (2323.452 ± 487.541) ng/ml in patients of the G3 group, and (796.616 ± 403.845) ng/ml in the healthy group as a control group.…”

Targeting Ferroptosis Attenuates Inflammation, Fibrosis, and Mast Cell Activation in Chronic Prostatitis

“…Iron chelator DFO and free radical scavenger EDA prevent ferroptosis by reducing iron availability and lipid peroxidation. 9 Journal of Immunology Research [17]. In the current study, the EAP model was developed in the similar method.…”

P. gingivalis in oral-prostate axis exacerbates benign prostatic hyperplasia via IL-6/IL-6R pathway

“…The long disease course, poor efficacy and heavy disease burden have seriously affected the quality of life of male patients worldwide [3]. BPH is a complex inflammatory disease, and a study has shown that inflammation plays a key role in the etiology of BPH [4]. Periodontitis is a chronic inflammatory disease, caused by destructive dental pathogens, has become a worldwide challenge [5][6][7][8].…”