Abstract

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.

中文翻译：

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Xist 减弱雌性细胞的急性炎症反应。

摘要

生理性别会影响炎症反应，因为男性的急性炎症和女性的慢性炎症发生率更高。在这里，我们报告说急性炎症被 X 失活特异性转录物 (Xist) 减弱，Xist 是一种对 X 染色体失活至关重要的女性细胞特异性核长非编码 RNA。脂多糖介导的急性炎症增加Xist雌性小鼠 J774A.1 巨噬细胞和人 AML193 单核细胞的细胞质中的水平。在这两种细胞类型中，细胞质 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，表明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 的表达显着降低了 IL-6 和 NF-κB 活性。表达 Xist 的雄性脾细胞的过继转移减少了雄性小鼠的急性爪肿胀，表明 Xist 可以具有保护性抗炎作用。这些发现表明 XIST 的功能超出了 X 染色体失活，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。