Xist attenuates acute inflammatory response by female cells.
Xist attenuates acute inflammatory response by female cells.
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DOI：
10.1007/s00018-020-03500-3
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Ajit SK
中科院分区：
文献类型：
--
作者：
Shenoda BB;Ramanathan S;Gupta R;Tian Y;Jean-Toussaint R;Alexander GM;Addya S;Somarowthu S;Sacan A;Ajit SK
生理性别影响炎症反应，因为男性急性炎症和女性慢性炎症的发病率更高。在这里，我们报告说，急性炎症是由X-失活特异性转录（Xist），一个女性细胞特异性核长非编码RNA X染色体失活至关重要的衰减。脂多糖介导的急性炎症增加了雌性小鼠J774A.1巨噬细胞和人AML 193单核细胞胞质中的Xist水平。在两种细胞类型中，胞质Xist与NF-κB的p65亚基共定位。这种相互作用与NF-κB核迁移减少有关，提示抑制急性炎症的新机制。进一步支持这一假设，雄性细胞中5' XIST的表达显著降低IL-6和NF-κB活性。表达Xist的雄性脾细胞的连续转移减少了雄性小鼠中的急性足肿胀，表明Xist可以具有保护性抗炎作用。这些发现表明，XIST具有超出X染色体失活的功能，并表明XIST可以通过减轻女性的急性炎症来促进炎症反应的性别特异性差异。
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.
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