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

研究成果: Article査読

15 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)645-654
ページ数10
ジャーナルMolecular Human Reproduction
21
8
DOI
出版ステータスPublished - 2015 3 10
外部発表はい

ASJC Scopus subject areas

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

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