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Placenta. 2014 Mar;35(3):152-62. doi: 10.1016/j.placenta.2013.12.013. Epub 2014 Jan 8.

Susceptibility to Toxoplasma gondii proliferation in BeWo human trophoblast cells is dose-dependent of macrophage migration inhibitory factor (MIF), via ERK1/2 phosphorylation and prostaglandin E2 production.

Author information

  • 1Laboratory of Histology and Embryology, Institute of Biomedical Sciences, Federal University of Uberlândia, Av. Pará, 1720, 38405-320 Uberlândia, MG, Brazil. Electronic address: bellisafb@icbim.ufu.br.
  • 2Department of Life Science, University of Siena, Aldo Moro Road 2, Siena, Italy. Electronic address: luana.riccipaulesu@unisi.it.
  • 3Department of Life Science, University of Siena, Aldo Moro Road 2, Siena, Italy. Electronic address: ietta@unisi.it.
  • 4Department of Life Science, University of Siena, Aldo Moro Road 2, Siena, Italy. Electronic address: nikoniko29@libero.it.
  • 5Department of Life Science, University of Siena, Aldo Moro Road 2, Siena, Italy. Electronic address: romagnolir@unisi.it.
  • 6Laboratory of Histology and Embryology, Institute of Biomedical Sciences, Federal University of Uberlândia, Av. Pará, 1720, 38405-320 Uberlândia, MG, Brazil. Electronic address: angellicagomes@yahoo.com.br.
  • 7Department of Biology, Cuesta College, Highway Road 1, San Luis Obispo, CA, United States. Electronic address: favoretojr@gmail.com.
  • 8Laboratory of Immunoparasitology, Institute of Biomedical Sciences, Federal University of Uberlândia, Av. Pará, 1720, 38405-320 Uberlândia, MG, Brazil. Electronic address: daosilva@yahoo.com.br.
  • 9Laboratory of Immunoparasitology, Institute of Biomedical Sciences, Federal University of Uberlândia, Av. Pará, 1720, 38405-320 Uberlândia, MG, Brazil. Electronic address: jrmineo@ufu.br.
  • 10Laboratory of Immunoparasitology, Institute of Biomedical Sciences, Federal University of Uberlândia, Av. Pará, 1720, 38405-320 Uberlândia, MG, Brazil. Electronic address: tiagomineo@gmail.com.
  • 11Laboratory of Histology and Embryology, Institute of Biomedical Sciences, Federal University of Uberlândia, Av. Pará, 1720, 38405-320 Uberlândia, MG, Brazil. Electronic address: eloisa@umuarama.ufu.br.

Abstract

INTRODUCTION:

Macrophage migration inhibitory factor (MIF) participates in the immune response to Toxoplasma gondii, triggers ERK1/2 and prostaglandin E2 (PGE2) activation, but there is limited information on these mechanisms in human trophoblast. The present study aimed to verify the role of MIF in the ERK1/2 phosphorylation and PGE2 production, as well as its effect on the susceptibility to T. gondii in BeWo cells.

METHODS:

BeWo cells were treated with increasing concentrations of recombinant MIF (rMIF) and/or T. gondii-soluble tachyzoite antigen (STAg) and analyzed for ERK1/2 phosphorylation and PGE2 production by Western blotting and ELISA, respectively. Cells were also treated with increasing concentrations of rMIF, rPGE2, or ERK1/2 inhibitor and tested for T. gondii proliferation. The supernatants of cells treated with rPGE2 were assayed for cytokine production by ELISA or CBA.

RESULTS:

ERK1/2 phosphorylation and PGE2 production increased when the cells were treated with low MIF concentrations while the parasitism control occurred only at high MIF concentrations. STAg was unable to change ERK1/2 phosphorylation or PGE2 release. BeWo cells demonstrated increased T. gondii proliferation and reduced production of pro-inflammatory cytokines when treated with PGE2, while PD98059 diminished the parasite proliferation.

DISCUSSION:

The intracellular mechanisms triggered by MIF are dose-dependent in BeWo cells, and PGE2 is an important factor for the persistence of T. gondii at the maternal fetal interface.

CONCLUSION:

MIF was unable to control T. gondii infection in BeWo cells at low concentrations since ERK1/2 and PGE2 expression were activated, demonstrating a critical effect of these mediators favoring parasite proliferation.

Copyright © 2014 Elsevier Ltd. All rights reserved.

KEYWORDS:

ERK1/2; MIF; PGE(2); Toxoplasma gondii; Trophoblast cells

PMID:
24433846
[PubMed - indexed for MEDLINE]
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