Background. The immune mechanisms underlying low-intensity ultrasound- (LIUS-) mediated suppression of inflammation and tumorigenesis remain poorly determined. Methods. We used microarray datasets from the NCBI GEO DataSet repository and conducted comprehensive data-mining analyses, where we examined the gene expression of 1376 innate immune regulators (innatome genes (IGs) in cells treated with LIUS. Results. We made the following findings: (1) LIUS upregulates proinflammatory IGs and downregulates metastasis genes in cancer cells, and LIUS upregulates adaptive immunity pathways but inhibits danger-sensing and inflammation pathways and promote tolerogenic differentiation in bone marrow (BM) cells. (2) LIUS upregulates IGs encoded for proteins localized in the cytoplasm, extracellular space, and others, but downregulates IG proteins localized in nuclear and plasma membranes, and LIUS downregulates phosphatases. (3) LIUS-modulated IGs act partially via several important pathways of reactive oxygen species (ROS), reverse signaling of immune checkpoint receptors B7-H4 and BTNL2, inflammatory cytokines, and static or oscillatory shear stress and heat generation, among which ROS is a dominant mechanism. (4) LIUS upregulates trained immunity enzymes in lymphoma cells and downregulates trained immunity enzymes and presumably establishes trained tolerance in BM cells. (5) LIUS modulates chromatin long-range interactions to differentially regulate IGs expression in cancer cells and noncancer cells. Conclusions. Our analysis suggests novel molecular mechanisms that are utilized by LIUS to induce tumor suppression and inflammation inhibition. Our findings may lead to development of new treatment protocols for cancers and chronic inflammation.

中文翻译：

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超声可以通过活性氧、免疫检查点、细胞因子和训练的免疫/耐受途径重塑内部组织来抑制肿瘤生长、抑制炎症并建立耐受性

背景。低强度超声（LIUS）介导的炎症和肿瘤发生抑制的免疫机制仍不清楚。方法。我们使用 NCBI GEO数据集存储库中的微阵列数据集并进行了全面的数据挖掘分析，其中我们检查了 LIUS 处理的细胞中 1376 个先天免疫调节因子（固有组基因 (IG)）的基因表达。。我们发现：(1) LIUS 上调促炎性 IG 并下调癌细胞中的转移基因，LIUS 上调适应性免疫途径，但抑制危险感知和炎症途径，并促进骨髓 (BM) 细胞的耐受性分化。(2) LIUS上调编码定位于细胞质、细胞外空间等的蛋白质的IG，但下调定位于核膜和质膜的IG蛋白，并且LIUS下调磷酸酶。(3) LIUS 调节的 IG 部分通过活性氧 (ROS)、免疫检查点受体 B7-H4 和 BTNL2 的反向信号传导、炎症细胞因子以及静态或振荡剪切应力和热量产生的几个重要途径发挥作用，其中 ROS 是主导机制。(4) LIUS 上调淋巴瘤细胞中经过训练的免疫酶并下调经过训练的免疫酶，并可能在 BM 细胞中建立经过训练的耐受性。(5) LIUS 调节染色质长程相互作用，以差异调节癌细胞和非癌细胞中的 IG 表达。结论。我们的分析表明 LIUS 利用新的分子机制来诱导肿瘤抑制和炎症抑制。我们的发现可能会导致癌症和慢性炎症新治疗方案的开发。