Next Article in Journal
miRNA-34c Overexpression Causes Dendritic Loss and Memory Decline
Next Article in Special Issue
Gosha-Jinki-Gan Recovers Spermatogenesis in Mice with Busulfan-Induced Aspermatogenesis
Previous Article in Journal
Trans-Ferulic Acid-4-β-Glucoside Alleviates Cold-Induced Oxidative Stress and Promotes Cold Tolerance
Article Menu
Issue 8 (August) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2018, 19(8), 2322;

Aggregation of Human Trophoblast Cells into Three-Dimensional Culture System Enhances Anti-Inflammatory Characteristics through Cytoskeleton Regulation

Laboratory of Animal Reproduction, Department of Animal Science, Tokyo University of Agriculture, Atsugi, Kanagawa 243-0034, Japan
NODAI Genome Research Center, Tokyo University of Agriculture, Setagaya, Tokyo 154-0017, Japan
Department of Obstetrics and Gynecology, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan
Author to whom correspondence should be addressed.
Received: 16 July 2018 / Revised: 3 August 2018 / Accepted: 6 August 2018 / Published: 8 August 2018
(This article belongs to the Special Issue Reproductive Immunology: Cellular and Molecular Biology)
Full-Text   |   PDF [2940 KB, uploaded 8 August 2018]   |  


Background: Three-dimensional (3D) culture changes cell characteristics and function, suggesting that 3D culture provides a more physiologically relevant environment for cells compared with 2D culture. We investigated the differences in cell functions depending on the culture model in human trophoblast cells (Sw.71). Methods: Sw.71 cells were incubated in 2D monolayers or simple 3D spheroids. After incubation, cells were corrected to assess RNA-seq transcriptome or protein expression, and culture medium were corrected to detect cytokines. To clarify the role of actin cytoskeleton, spheroid Sw.71 cells were treated mycalolide B (inhibitor of actin polymerization) in a 3D culture. Results: RNA-seq transcriptome analysis, results revealed that 3D-cultured cells had a different transcriptional profile compared with 2D-cultured cells, especially regarding inflammation-related molecules. Although interleukin-6 (IL-6) mRNA level was higher in 3D-culured cells, its secretion levels were higher in 2D-cultured cells. In addition, the levels of mRNA and protein expression of regnase-1, regulatory RNase of inflammatory cytokine, significantly increased in 3D culture, suggesting post-translational modification of IL-6 mRNA via regnase-1. Treatment with mycalolide B reduced cell-to-cell contact to build 3D formation and increased expression of actin cytoskeleton, resulting in increased IL-6 secretin. Conclusion: Cell dimensionality plays an essential role in governing the spatiotemporal cellular outcomes, including inflammatory cytokine production and its negative regulation associated with regnase-1. View Full-Text
Keywords: inflammation; interleukin-6; regnase-1; trophoblast cells inflammation; interleukin-6; regnase-1; trophoblast cells

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material


Share & Cite This Article

MDPI and ACS Style

Seno, K.; Munakata, Y.; Sano, M.; Kawahara-Miki, R.; Takahashi, H.; Ohkuchi, A.; Iwata, H.; Kuwayama, T.; Shirasuna, K. Aggregation of Human Trophoblast Cells into Three-Dimensional Culture System Enhances Anti-Inflammatory Characteristics through Cytoskeleton Regulation. Int. J. Mol. Sci. 2018, 19, 2322.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top