C-C motif chemokine ligand 2 regulates lps-induced inflammation and ER stress to enhance proliferation of bovine endometrial epithelial cells

J Cell Physiol. 2018 Apr;233(4):3141-3151. doi: 10.1002/jcp.26151. Epub 2017 Nov 10.

Abstract

Chemokines play an important role in regulating the complex immune system at the maternal-fetal interface during pregnancy. Among various chemokines, CC motif chemokine ligand 2 (CCL2) plays a role in the recruitment of immune regulatory cells to implantation sites within the endometrium. In cattle, CCL2 is abundantly expressed in the uterine endometrium. However, its intracellular signaling has not been identified. In this study, we examined the effects of CCL2 on bovine endometrial (BEND) cell proliferation. CCL2 stimulated BEND cell proliferation by abundant expression of PCNA, accumulation of cells in the G2/M phase, and activation of the PI3 K/AKT and MAPK signaling pathways. Moreover, CCL2 reduced endoplasmic reticulum stress and restored the inflammation-induced reduction in BEND cell proliferation by regulating the unfolded protein response genes and cytokines. Collectively, these results demonstrated that CCL2 plays a pivotal role in reproductive tissues and may support maternal-fetal interface to improve efficiency of pregnancy.

Keywords: CCL2; endometrial epithelial cells; endoplasmic reticulum stress; immune system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cattle
  • Cell Cycle / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Chemokine CCL2 / chemistry
  • Chemokine CCL2 / genetics
  • Endometrium / pathology*
  • Endoplasmic Reticulum Stress* / drug effects
  • Epithelial Cells / drug effects
  • Epithelial Cells / pathology*
  • Female
  • Inflammation / pathology*
  • Lipopolysaccharides / metabolism*
  • MAP Kinase Signaling System / drug effects
  • Models, Biological
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Sequence Analysis, DNA
  • Tunicamycin / pharmacology

Substances

  • Chemokine CCL2
  • Lipopolysaccharides
  • Tunicamycin
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt