Elevated Levels of ADMA Are Associated with Lower DDAH2 and Higher PRMT1 in LPS-Induced Endometritis Rats

Inflammation. 2018 Feb;41(1):299-306. doi: 10.1007/s10753-017-0687-1.

Abstract

Chronic endometritis is a continuous inflammation of uterine endometrium. Recent research has shown that higher asymmetric dimethylarginine (ADMA) levels contribute to endothelial dysfunction. In the present study, we tested whether there is a correlation between endometritis and ADMA in LPS-induced endometritis rat and the mechanisms involved. Thirty-six rats were divided into two groups: blank control group and rat model of endometritis group. The entire infused uterus were removed to observe the changes of histopathology, production of myeloperoxidase (MPO), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, 8-isoprostane, and reactive oxygen species (ROS), and gene expression of dimethylarginine dimethylaminohydrolase 2 (DDAH2), protein-methyl transferase 1 (PRMT1), TNF-α, and IL-6. In endometritis rat group, characteristic histopathologic changes in uteri were observed. The uterine 8-isoprostane, ROS, MPO activity, IL-6 and TNF-α concentrations, PRMT1, IL-6, and TNF-α expressions were significantly elevated, and DDAH2 expression was notably reduced in endometritis group compared with control group. The present findings suggest that elevated levels of ADMA are associated with lower DDAH2 and higher PRMT1 in LPS-induced endometritis rat.

Keywords: asymmetric dimethylarginine; dimethylarginine dimethylaminohydrolase 2; endometritis; protein-methyl transferase 1; rat.

MeSH terms

  • Amidohydrolases / genetics
  • Amidohydrolases / metabolism*
  • Animals
  • Arginine / analogs & derivatives*
  • Arginine / metabolism
  • Dinoprost / analogs & derivatives
  • Dinoprost / metabolism
  • Disease Models, Animal
  • Down-Regulation
  • Endometriosis / chemically induced
  • Endometriosis / enzymology*
  • Endometriosis / genetics
  • Endometriosis / pathology
  • Female
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Lipopolysaccharides*
  • Peroxidase / metabolism
  • Protein-Arginine N-Methyltransferases / genetics
  • Protein-Arginine N-Methyltransferases / metabolism*
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation
  • Uterus / enzymology*
  • Uterus / pathology

Substances

  • Interleukin-6
  • Lipopolysaccharides
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • lipopolysaccharide, E coli O55-B5
  • 8-epi-prostaglandin F2alpha
  • N,N-dimethylarginine
  • Arginine
  • Dinoprost
  • Peroxidase
  • PRMT1 protein, rat
  • Protein-Arginine N-Methyltransferases
  • Amidohydrolases
  • dimethylargininase