Open AccessXist attenuates acute inflammatory response by female cells
Author(s) -
Botros Shenoda,
Sujay Ramanathan,
Richa Gupta,
Yadong Tian,
Renée JeanToussaint,
Guillermo M. Alexander,
Sankar Addya,
Srinivas Somarowthu,
Ahmet Saçan,
Seena K. Ajit
Publication year - 2020
Publication title -
cellular and molecular life sciences (print)
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.928
H-Index - 223
eISSN - 1420-9071
pISSN - 1420-682X
DOI - 10.1007/s00018-020-03500-3
Subject(s) - xist , inflammation , x inactivation , biology , lipopolysaccharide , immunology , microbiology and biotechnology , long non coding rna , nf κb , x chromosome , rna , genetics , gene
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.