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Xist attenuates acute inflammatory response by female cells
Journal article   Open access   Peer reviewed

Xist attenuates acute inflammatory response by female cells

Botros B Shenoda, Sujay Ramanathan, Richa Gupta, Yuzhen Tian, Renee Jean-Toussaint, Guillermo M Alexander, Sankar Addya, Srinivas Somarowthu, Ahmet Sacan and Seena K Ajit
Cellular and molecular life sciences : CMLS, v 78(1), pp 299-316
Jan 2021
DOI: https://doi.org/10.1007/s00018-020-03500-3
PMID: 32193609
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501270View
Accepted (AM)Open Access (License Unspecified),  Open

Abstract

Animals Cells, Cultured Cytoplasm - metabolism Female Gene Expression Regulation Humans Inflammation - metabolism Inflammation - pathology Inflammation - prevention & control Interleukin-6 - genetics Interleukin-6 - metabolism Lipopolysaccharides - pharmacology Macrophages - cytology Macrophages - drug effects Macrophages - metabolism Male Mice Mice, Inbred C57BL Monocytes - cytology Monocytes - metabolism NF-kappa B - metabolism RNA Interference RNA, Long Noncoding - antagonists & inhibitors RNA, Long Noncoding - genetics RNA, Long Noncoding - metabolism RNA, Small Interfering - metabolism Sex Factors Transcription Factor RelA - metabolism
Biological sex influences inflammatory response, as there is a greater incidence of acute inflammation in men and chronic inflammation in women. Here, we report that acute inflammation is attenuated by X-inactive specific transcript (Xist), a female cell-specific nuclear long noncoding RNA crucial for X-chromosome inactivation. Lipopolysaccharide-mediated acute inflammation increased Xist levels in the cytoplasm of female mouse J774A.1 macrophages and human AML193 monocytes. In both cell types, cytoplasmic Xist colocalizes with the p65 subunit of NF-κB. This interaction was associated with reduced NF-κB nuclear migration, suggesting a novel mechanism to suppress acute inflammation. Further supporting this hypothesis, expression of 5' XIST in male cells significantly reduced IL-6 and NF-κB activity. Adoptive transfer of male splenocytes expressing Xist reduced acute paw swelling in male mice indicating that Xist can have a protective anti-inflammatory effect. These findings show that XIST has functions beyond X chromosome inactivation and suggest that XIST can contribute to sex-specific differences underlying inflammatory response by attenuating acute inflammation in women.

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33 citations in Web of Science
30 citations in Scopus

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UN Sustainable Development Goals (SDGs)

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#3 Good Health and Well-Being

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Collaboration types
Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
Cell Biology
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