Regulated C-C motif ligand 2 (CCL2) in luteal cells contributes to macrophage infiltration into the human corpus luteum during luteolysis

Junko Nio-Kobayashi, Masataka Kudo, Noriaki Sakuragi, Shunsuke Kimura, Toshihiko Iwanaga, W. Colin Duncan

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Intense macrophage infiltration is observed during luteolysis in various animals including women; however, we still do not know how macrophage infiltration into the human corpus luteum (CL) during luteolysis is regulated. In this study, we examined the expression, localization and regulation of an important chemokine for the recruitment of monocyte/macrophage lineages,C-Cmotif ligand 2 (CCL2), in thehuman CL across the luteal phase and in cultured human luteinized granulosa cells (LGCs), with special reference to the number of infiltrating macrophages and luteal cell function. CCL2 mRNA increased in the non-functional regressing CL during menstruation (P < 0.01), corresponding to an elevated mRNA expression of a macrophage-derived cytokine, tumor necrosis factor (TNF), and an increased number of infiltrating macrophages positively stained with a macrophage marker, CD68. CCL2 protein was immunohistochemically localized to the cytoplasm of granulosalutein and theca-lutein cells, and CCL2mRNAwas significantly reduced byhCGboth in vivo (P < 0.05) and in vitro (P < 0.01). CCL2 was also downregulated by luteotrophic prostaglandin (PG) E (P < 0.0001), but up-regulated by luteolytic PGF (P < 0.05) in vitro. Administration of TNF significantly enhanced the CCL2 mRNA expression in cultured LGCs (P < 0.01). A greater abundance of infiltrating macrophages were found around granulosa-lutein cells lacking 3b-HSD or PGE synthase (PGES) immunostaining. CCL2 mRNA expression was negatively correlated with both HSD3B1 and PGES, suggesting that locally produced progesterone and PGE suppress macrophage infiltration into the CL. Taken together, the infiltrationofmacrophages inthe humanCL is regulated byendocrine and paracrinemolecules via regulationof theCCL2 expression inluteal cells.

Original languageEnglish
Pages (from-to)645-654
Number of pages10
JournalMolecular Human Reproduction
Volume21
Issue number8
DOIs
Publication statusPublished - 2015 Mar 10
Externally publishedYes

Fingerprint

Luteolysis
Luteal Cells
Corpus Luteum
Macrophages
Ligands
Prostaglandins E
Messenger RNA
Granulosa Cells
Tumor Necrosis Factor-alpha
Menstruation
Luteal Phase
Prostaglandins F
Chemokines
Progesterone
Monocytes
Cytoplasm
Down-Regulation
Cytokines

Keywords

  • CCL2
  • Human corpus luteum
  • Macrophage
  • PGE
  • Progesterone

ASJC Scopus subject areas

  • Reproductive Medicine
  • Embryology
  • Molecular Biology
  • Genetics
  • Obstetrics and Gynaecology
  • Developmental Biology
  • Cell Biology

Cite this

Regulated C-C motif ligand 2 (CCL2) in luteal cells contributes to macrophage infiltration into the human corpus luteum during luteolysis. / Nio-Kobayashi, Junko; Kudo, Masataka; Sakuragi, Noriaki; Kimura, Shunsuke; Iwanaga, Toshihiko; Colin Duncan, W.

In: Molecular Human Reproduction, Vol. 21, No. 8, 10.03.2015, p. 645-654.

Research output: Contribution to journalArticle

Nio-Kobayashi, Junko ; Kudo, Masataka ; Sakuragi, Noriaki ; Kimura, Shunsuke ; Iwanaga, Toshihiko ; Colin Duncan, W. / Regulated C-C motif ligand 2 (CCL2) in luteal cells contributes to macrophage infiltration into the human corpus luteum during luteolysis. In: Molecular Human Reproduction. 2015 ; Vol. 21, No. 8. pp. 645-654.
@article{d5e99cad18db4fdbb78e05f8d93ee706,
title = "Regulated C-C motif ligand 2 (CCL2) in luteal cells contributes to macrophage infiltration into the human corpus luteum during luteolysis",
abstract = "Intense macrophage infiltration is observed during luteolysis in various animals including women; however, we still do not know how macrophage infiltration into the human corpus luteum (CL) during luteolysis is regulated. In this study, we examined the expression, localization and regulation of an important chemokine for the recruitment of monocyte/macrophage lineages,C-Cmotif ligand 2 (CCL2), in thehuman CL across the luteal phase and in cultured human luteinized granulosa cells (LGCs), with special reference to the number of infiltrating macrophages and luteal cell function. CCL2 mRNA increased in the non-functional regressing CL during menstruation (P < 0.01), corresponding to an elevated mRNA expression of a macrophage-derived cytokine, tumor necrosis factor (TNF), and an increased number of infiltrating macrophages positively stained with a macrophage marker, CD68. CCL2 protein was immunohistochemically localized to the cytoplasm of granulosalutein and theca-lutein cells, and CCL2mRNAwas significantly reduced byhCGboth in vivo (P < 0.05) and in vitro (P < 0.01). CCL2 was also downregulated by luteotrophic prostaglandin (PG) E (P < 0.0001), but up-regulated by luteolytic PGF (P < 0.05) in vitro. Administration of TNF significantly enhanced the CCL2 mRNA expression in cultured LGCs (P < 0.01). A greater abundance of infiltrating macrophages were found around granulosa-lutein cells lacking 3b-HSD or PGE synthase (PGES) immunostaining. CCL2 mRNA expression was negatively correlated with both HSD3B1 and PGES, suggesting that locally produced progesterone and PGE suppress macrophage infiltration into the CL. Taken together, the infiltrationofmacrophages inthe humanCL is regulated byendocrine and paracrinemolecules via regulationof theCCL2 expression inluteal cells.",
keywords = "CCL2, Human corpus luteum, Macrophage, PGE, Progesterone",
author = "Junko Nio-Kobayashi and Masataka Kudo and Noriaki Sakuragi and Shunsuke Kimura and Toshihiko Iwanaga and {Colin Duncan}, W.",
year = "2015",
month = "3",
day = "10",
doi = "10.1093/molehr/gav028",
language = "English",
volume = "21",
pages = "645--654",
journal = "Molecular Human Reproduction",
issn = "1360-9947",
publisher = "Oxford University Press",
number = "8",

}

TY - JOUR

T1 - Regulated C-C motif ligand 2 (CCL2) in luteal cells contributes to macrophage infiltration into the human corpus luteum during luteolysis

AU - Nio-Kobayashi, Junko

AU - Kudo, Masataka

AU - Sakuragi, Noriaki

AU - Kimura, Shunsuke

AU - Iwanaga, Toshihiko

AU - Colin Duncan, W.

PY - 2015/3/10

Y1 - 2015/3/10

N2 - Intense macrophage infiltration is observed during luteolysis in various animals including women; however, we still do not know how macrophage infiltration into the human corpus luteum (CL) during luteolysis is regulated. In this study, we examined the expression, localization and regulation of an important chemokine for the recruitment of monocyte/macrophage lineages,C-Cmotif ligand 2 (CCL2), in thehuman CL across the luteal phase and in cultured human luteinized granulosa cells (LGCs), with special reference to the number of infiltrating macrophages and luteal cell function. CCL2 mRNA increased in the non-functional regressing CL during menstruation (P < 0.01), corresponding to an elevated mRNA expression of a macrophage-derived cytokine, tumor necrosis factor (TNF), and an increased number of infiltrating macrophages positively stained with a macrophage marker, CD68. CCL2 protein was immunohistochemically localized to the cytoplasm of granulosalutein and theca-lutein cells, and CCL2mRNAwas significantly reduced byhCGboth in vivo (P < 0.05) and in vitro (P < 0.01). CCL2 was also downregulated by luteotrophic prostaglandin (PG) E (P < 0.0001), but up-regulated by luteolytic PGF (P < 0.05) in vitro. Administration of TNF significantly enhanced the CCL2 mRNA expression in cultured LGCs (P < 0.01). A greater abundance of infiltrating macrophages were found around granulosa-lutein cells lacking 3b-HSD or PGE synthase (PGES) immunostaining. CCL2 mRNA expression was negatively correlated with both HSD3B1 and PGES, suggesting that locally produced progesterone and PGE suppress macrophage infiltration into the CL. Taken together, the infiltrationofmacrophages inthe humanCL is regulated byendocrine and paracrinemolecules via regulationof theCCL2 expression inluteal cells.

AB - Intense macrophage infiltration is observed during luteolysis in various animals including women; however, we still do not know how macrophage infiltration into the human corpus luteum (CL) during luteolysis is regulated. In this study, we examined the expression, localization and regulation of an important chemokine for the recruitment of monocyte/macrophage lineages,C-Cmotif ligand 2 (CCL2), in thehuman CL across the luteal phase and in cultured human luteinized granulosa cells (LGCs), with special reference to the number of infiltrating macrophages and luteal cell function. CCL2 mRNA increased in the non-functional regressing CL during menstruation (P < 0.01), corresponding to an elevated mRNA expression of a macrophage-derived cytokine, tumor necrosis factor (TNF), and an increased number of infiltrating macrophages positively stained with a macrophage marker, CD68. CCL2 protein was immunohistochemically localized to the cytoplasm of granulosalutein and theca-lutein cells, and CCL2mRNAwas significantly reduced byhCGboth in vivo (P < 0.05) and in vitro (P < 0.01). CCL2 was also downregulated by luteotrophic prostaglandin (PG) E (P < 0.0001), but up-regulated by luteolytic PGF (P < 0.05) in vitro. Administration of TNF significantly enhanced the CCL2 mRNA expression in cultured LGCs (P < 0.01). A greater abundance of infiltrating macrophages were found around granulosa-lutein cells lacking 3b-HSD or PGE synthase (PGES) immunostaining. CCL2 mRNA expression was negatively correlated with both HSD3B1 and PGES, suggesting that locally produced progesterone and PGE suppress macrophage infiltration into the CL. Taken together, the infiltrationofmacrophages inthe humanCL is regulated byendocrine and paracrinemolecules via regulationof theCCL2 expression inluteal cells.

KW - CCL2

KW - Human corpus luteum

KW - Macrophage

KW - PGE

KW - Progesterone

UR - http://www.scopus.com/inward/record.url?scp=84939508042&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84939508042&partnerID=8YFLogxK

U2 - 10.1093/molehr/gav028

DO - 10.1093/molehr/gav028

M3 - Article

VL - 21

SP - 645

EP - 654

JO - Molecular Human Reproduction

JF - Molecular Human Reproduction

SN - 1360-9947

IS - 8

ER -