Extracorporeal shock wave therapy decreases COX-2 by inhibiting TLR4-NFκB pathway in a prostatitis rat model

Prostate. 2019 Sep;79(13):1498-1504. doi: 10.1002/pros.23880. Epub 2019 Aug 2.

Abstract

Background: This study aims to evaluate the effect of extracorporeal shock wave therapy (ESWT) on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and to explore the mechanism.

Methods: RWPE-2 cells were randomly divided into three groups: (a) RWPE-2 group (normal control), (b) LPS groups (lipopolysaccharide inducing inflammation) and (c) ESWT groups (LPS induced RWPE-2 treated by ESWT). After ESWT was administered, cells and supernatant were collected for enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. In vivo, Sprague-Dawley rats (n = 30) were randomly divided into three groups: (a) normal control group, (b) prostatitis groups, and (c) ESWT groups. Prostatitis rats were induced by 17 β-estradiol and dihydrotestosterone for 4 weeks. After ESWT, prostates of each group were collected for immunohistochemistry, Western blot analysis, and ELISA.

Results: ESWT improved prostatitis by attenuating inflammation (P < .01). ESWT downregulated the expression of cyclooxygenase 2 (COX-2) through inhibiting TLR4-NFκB pathway compared with the LPS group in vitro or prostatitis group in vivo (P < .05). TRAF2 mediates ERK1/2-COX2 pathway. ESWT promotes prostate tissue recovery by stimulating vascular endothelial growth factor expression (P < .01). ESWT could suppress apoptosis in the prostate.

Conclusions: ESWT improved CP/CPPS and reduced inflammation by degrading COX-2 in microenvironment through TLR4-NFκB-inhibiting pathway. TRAF2 regulator in ERK1/2-COX-2 inhibition significantly reduced inflammation, thus suggesting ESWT may be a potential and promising treatment for CP/CPPS.

Keywords: RWPE-2; chronic pelvic pain syndrome; chronic prostatitis; low-energy shock wave therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Cell Line
  • Chronic Disease
  • Cyclooxygenase 2 / metabolism*
  • Down-Regulation
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Extracorporeal Shockwave Therapy*
  • Male
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Pelvic Pain / metabolism
  • Pelvic Pain / pathology
  • Pelvic Pain / therapy
  • Prostatitis / metabolism
  • Prostatitis / pathology
  • Prostatitis / therapy*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • TNF Receptor-Associated Factor 2 / metabolism
  • Toll-Like Receptor 4 / antagonists & inhibitors
  • Toll-Like Receptor 4 / metabolism*
  • Vascular Endothelial Growth Factor A / biosynthesis

Substances

  • NF-kappa B
  • TNF Receptor-Associated Factor 2
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat
  • Cyclooxygenase 2
  • Ptgs2 protein, rat
  • Extracellular Signal-Regulated MAP Kinases