Landscape of electrophilic and inflammatory stress-mediated gene regulation in human lymphoblastoid cell lines

Noriko Ishida; Yuichi Aoki; Fumiki Katsuoka; Ichiko Nishijima; Takahiro Nobukuni; Hayato Anzawa; Li Bin; Miyuki Tsuda; Kazuki Kumada; Hisaaki Kudo; Takahiro Terakawa; Akihito Otsuki; Kengo Kinoshita; Riu Yamashita; Naoko Minegishi; Masayuki Yamamoto

doi:10.1016/j.freeradbiomed.2020.09.023

Landscape of electrophilic and inflammatory stress-mediated gene regulation in human lymphoblastoid cell lines

Free Radic Biol Med. 2020 Dec:161:71-83. doi: 10.1016/j.freeradbiomed.2020.09.023. Epub 2020 Oct 2.

Authors

Affiliations

¹ Department of Biobank, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Miyagi, Japan.
² Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Miyagi, Japan; Department of System Bioinformatics, Graduate School of Information Sciences, Tohoku University, Sendai, Japan.
³ Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Miyagi, Japan.
⁴ Department of System Bioinformatics, Graduate School of Information Sciences, Tohoku University, Sendai, Japan.
⁵ Department of Biobank, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Miyagi, Japan; Advanced Research Center for Innovations in Next Generation Medicine, Tohoku University, Sendai, Miyagi, Japan.
⁶ Department of Biobank, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Miyagi, Japan; Division of Translational Informatics, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
⁷ Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Miyagi, Japan; Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. Electronic address: [email protected].

PMID: 33011271
DOI: 10.1016/j.freeradbiomed.2020.09.023

Abstract

Human lymphoblastoid cell lines (LCLs) are valuable for the functional analyses of diseases. We have established more than 4200 LCLs as one of the resources of an integrated biobank. While oxidative and inflammatory stresses play critical roles in the onset and progression of various diseases, the responsiveness of LCLs, especially that of biobank-made LCLs, to these stresses has not been established. To address how LCLs respond to these stresses, in this study, we performed RNA sequencing of eleven human LCLs that were treated with an electrophile, diethyl maleate (DEM) and/or an inflammatory mediator, lipopolysaccharide (LPS). We found that over two thousand genes, including those regulated by a master regulator of the electrophilic/oxidative stress response, NRF2, were upregulated in LCLs treated with DEM, while approximately three hundred genes, including inflammation-related genes, were upregulated in LPS-treated LCLs. Of the LPS-induced genes, a subset of proinflammatory genes was repressed by DEM, supporting the notion that DEM suppresses the expression of proinflammatory genes through NRF2 activation. Conversely, a part of DEM-induced gene was repressed by LPS, suggesting reciprocal interference between electrophilic and inflammatory stress-mediated pathways. These data clearly demonstrate that LCLs maintain, by and large, responsive pathways against oxidative and inflammatory stresses and further endorse the usefulness of the LCL supply from the biobank.

Keywords: Electrophilic stress; Inflammatory stress; LCL; NRF2.

Publication types

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

MeSH terms

Cell Line
Gene Expression Regulation*
Humans
Oxidation-Reduction
Oxidative Stress* / genetics
Sequence Analysis, RNA