Mitigation of ER-stress and inflammation by chemokine (C-C motif) ligand 21 during early pregnancy

Hyocheol Bae; Whasun Lim; Fuller W Bazer; Kwang-Youn Whang; Gwonhwa Song

doi:10.1016/j.dci.2019.01.016

Mitigation of ER-stress and inflammation by chemokine (C-C motif) ligand 21 during early pregnancy

Dev Comp Immunol. 2019 May:94:73-84. doi: 10.1016/j.dci.2019.01.016. Epub 2019 Jan 31.

Authors

Hyocheol Bae¹, Whasun Lim², Fuller W Bazer³, Kwang-Youn Whang⁴, Gwonhwa Song⁵

Affiliations

¹ Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea.
² Department of Food and Nutrition, College of Science and Technology, Kookmin University, Seoul, 02707, Republic of Korea.
³ Center for Animal Biotechnology and Genomics and Department of Animal Science, Texas A&M University, College Station, 77843-2471, Texas, USA.
⁴ Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea. Electronic address: kwhang@korea.ac.kr.
⁵ Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea. Electronic address: ghsong@korea.ac.kr.

PMID: 30711450
DOI: 10.1016/j.dci.2019.01.016

Abstract

The immune system plays an important role in pregnancy. Chemokines recruit leukocytes at the maternal-fetal interface during early pregnancy. However, the role of the chemokine, C-C motif chemokine ligand 21 (CCL21), is less known. The aim of this study was to identify the expression of CCL21 and its receptor, CCR7, in the endometrium during estrous cycle and early pregnancy, and to investigate the functional effects of CCL21 on porcine trophectoderm (pTr) and porcine uterine luminal epithelial (pLE) cells. Our results indicated that CCL21 and CCR7 are increased in the glandular (GE) and luminal epithelium (LE) of the endometrium during early pregnancy, compared to estrous pigs. Recombinant CCL21 improved pTr and pLE cell proliferation through activation of the PI3K and MAPK pathways and suppression of tunicamycin-induced endoplasmic reticulum (ER) stress or LPS-induced inflammation. Collectively, these results provide novel insights into CCL21-mediated signaling mechanisms at the maternal-fetal interface during early pregnancy.

Keywords: CCL21; CCR7; Development; Pigs; Pregnancy; Uterus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Proliferation
Cells, Cultured
Chemokine CCL21 / genetics*
Chemokine CCL21 / metabolism
Endometrium / physiology*
Endoplasmic Reticulum Stress / immunology*
Epithelial Cells / physiology*
Estrous Cycle
Female
Inflammation / immunology*
Lipopolysaccharides / immunology
Mitogen-Activated Protein Kinases / metabolism
Phosphatidylinositol 3-Kinases / metabolism
Pregnancy / immunology*
Receptors, CCR7 / genetics*
Receptors, CCR7 / metabolism
Signal Transduction
Swine
Tunicamycin

Substances

Chemokine CCL21
Lipopolysaccharides
Receptors, CCR7
Tunicamycin
Phosphatidylinositol 3-Kinases
Mitogen-Activated Protein Kinases