Neuromedin B mediates IL-6 and COX-2 expression through NF-κB/P65 and AP-1/C-JUN activation in human primary myometrial cells

Biosci Rep. 2019 Oct 30;39(10):BSR20192139. doi: 10.1042/BSR20192139.

Abstract

Neuromedin B (NMB) and its receptor regulate labor onset by mediating inflammatory factors; however the underlying mechanisms remain poorly understood. The present study is aimed to investigate the mechanisms of NMB-induced cyclo-oxygenase 2 (COX-2) expression and interleukin (IL)-6 generation in human primary myometrial cells. The results indicated that NMB could increase phosphorylation of nuclear factor κB (NF-κB) transcription factor p65 (p65) and Jun proto-oncogene, activator protein 1 (AP-1) transcription factor subunit (c-Jun), and in turn, markedly up-regulated the expression levels of COX-2 and IL-6. This up-regulation was significantly attenuated by knockdown of p65 or c-Jun, and enhanced by overexpression of p65 or c-Jun. Furthermore, we identified a potential interaction between p65 and c-Jun following NMB stimulation. In addition, a significant positive correlation was observed between the amount of phosphorylated p65 and the levels of COX-2 and IL-6, and between the amount of phosphorylated c-Jun and COX-2 and IL-6 levels. These data suggested that NMB-induced COX-2 and IL-6 expression were mediated via p65 and c-Jun activation.

Keywords: AP-1/c-Jun; COX-2; IL-6; NF-κB/p65; human primary myometrial cells; neuromedin B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cells, Cultured
  • Cyclooxygenase 2 / biosynthesis*
  • Female
  • Gene Expression Regulation / drug effects*
  • Humans
  • Interleukin-6 / biosynthesis*
  • Myometrium / metabolism*
  • Neurokinin B / analogs & derivatives*
  • Neurokinin B / pharmacology
  • Pregnancy
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-jun / metabolism*
  • Transcription Factor AP-1 / metabolism*
  • Transcription Factor RelA / metabolism*

Substances

  • IL6 protein, human
  • Interleukin-6
  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-jun
  • RELA protein, human
  • Transcription Factor AP-1
  • Transcription Factor RelA
  • Neurokinin B
  • neuromedin B
  • Cyclooxygenase 2
  • PTGS2 protein, human