Alternative Titleマクロファージはクロストーク機構により子宮内膜細胞を酸化ストレスから保護する
Note (General)type:Thesis
This aim of this study was to investigate whether macrophages protect endometriotic cells from oxidative injury and to elucidate the underlying mechanisms of any protection. Endometriotic cells cultured with or without differentiated macrophages (dTHP-1 cells) were treated with hydrogen peroxide (H2O2) or methemoglobin, a major component of hemoglobin species in endometriotic cyst fluid. Co-culture experiments, microarray analysis, screening and validation of differentially expressed genes (DEGs), cell proliferation and viability assays, and experiments using a specific inhibitor were conducted to investigate the functional cross-talk between endometriotic cells and macrophages. Microarray analysis revealed that endometriotic cells co-cultured with dTHP-1 differentially express several genes compared with monoculture. Quantitative enzyme-linked immunosorbent assay (ELISA) and Western blotting analysis identified TGF-β1 as a promising candidate gene expressed in endometriotic cells co-cultured with dTHP-1 cells. TGF-β1 stimulated the expression of heme oxygenase-1 (HO-1) in dTHP-1 cells. HO-1 expression was increased in dTHP-1 cells co-cultured with endometriotic cells compared with the dTHP-1 monoculture. Both H2O2 and methemoglobin upregulated the expression of the HO-1 protein in the dTHP-1 monoculture; moreover, co-culture with endometriotic cells further enhanced HO-1 production. The co-culture with dTHP-1 protected endometriotic cells against oxidative injury. Blockade of HO-1 abolished the protective effects of macrophages. In an oxidative stress environment, TGF-β1 produced by endometriotic cells may protect against oxidative injury through the upregulation of macrophage-derived HO-1. The cross-talk between endometriotic cells and macrophages may contribute to the progression and pathogenesis of endometriosis.
博士(医学)・甲第849号・令和4年9月28日
Copyright © 2022, Society for Reproductive Investigation.
© 2022 Springer Nature Switzerland AG.
The version of record of this article, first published in Reproductive Sciences, is available online at Publisher's website: https://doi.org/10.1007/s43032-022-00890-6.
identifier:Reproductive sciences Vol.29 No.8 p.2165-2178 (2022 Aug)
identifier:19337191
identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/4076
identifier:Reproductive sciences, 29(8): 2165-2178
Collection (particular)国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文
Date Accepted (W3CDTF)2024-03-01T22:05:19+09:00
Data Provider (Database)国立国会図書館 : 国立国会図書館デジタルコレクション