Xist attenuates acute inflammatory response by female cells
| Autor: | Ahmet Sacan, Yuzhen Tian, Srinivas Somarowthu, Botros B. Shenoda, Seena K. Ajit, Renee Jean-Toussaint, Richa Gupta, Sankar Addya, Guillermo M. Alexander, Sujay Ramanathan |
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| Rok vydání: | 2019 |
| Předmět: |
Lipopolysaccharides
Male Cell type Adoptive cell transfer Cytoplasm Inflammation Biology X-inactivation Monocytes Article 03 medical and health sciences Cellular and Molecular Neuroscience Mice Sex Factors medicine Splenocyte Animals Humans RNA Small Interfering Molecular Biology Cells Cultured Pharmacology 0303 health sciences Interleukin-6 Macrophages 030302 biochemistry & molecular biology NF-kappa B Transcription Factor RelA Cell Biology Long non-coding RNA Mice Inbred C57BL Gene Expression Regulation Cancer research Molecular Medicine XIST Female RNA Interference RNA Long Noncoding medicine.symptom |
| Zdroj: | Cell Mol Life Sci |
| ISSN: | 1420-9071 |
| Popis: | 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 macrophage cells and human AML193 monocyte. 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. |
| Databáze: | OpenAIRE |
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