Ultrasound May Suppress Tumor Growth, Inhibit Inflammation, and Establish Tolerogenesis by Remodeling Innatome via Pathways of ROS, Immune Checkpoints, Cytokines, and Trained Immunity/Tolerance
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 examine...
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Wiley
2021-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2021/6664453 |
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| author | Qian Yang Ruijing Zhang Peng Tang Yu Sun Candice Johnson Jason Saredy Susu Wu Jiwei Wang Yifan Lu Fatma Saaoud Ying Shao Charles Drummer Keman Xu Daohai Yu Rongshan Li Shuping Ge Xiaohua Jiang Hong Wang Xiaofeng Yang |
| author_facet | Qian Yang Ruijing Zhang Peng Tang Yu Sun Candice Johnson Jason Saredy Susu Wu Jiwei Wang Yifan Lu Fatma Saaoud Ying Shao Charles Drummer Keman Xu Daohai Yu Rongshan Li Shuping Ge Xiaohua Jiang Hong Wang Xiaofeng Yang |
| author_sort | Qian Yang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-3c1e2025dcda46cb97274d331952f0e6 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
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| series | Journal of Immunology Research |
| spelling | doaj-art-3c1e2025dcda46cb97274d331952f0e62025-02-03T01:20:48ZengWileyJournal of Immunology Research2314-88612314-71562021-01-01202110.1155/2021/66644536664453Ultrasound May Suppress Tumor Growth, Inhibit Inflammation, and Establish Tolerogenesis by Remodeling Innatome via Pathways of ROS, Immune Checkpoints, Cytokines, and Trained Immunity/ToleranceQian Yang0Ruijing Zhang1Peng Tang2Yu Sun3Candice Johnson4Jason Saredy5Susu Wu6Jiwei Wang7Yifan Lu8Fatma Saaoud9Ying Shao10Charles Drummer11Keman Xu12Daohai Yu13Rongshan Li14Shuping Ge15Xiaohua Jiang16Hong Wang17Xiaofeng Yang18Centers for Cardiovascular Research and Inflammation, Translational, & Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USACenters for Cardiovascular Research and Inflammation, Translational, & Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USADepartment of Orthopedics, Beijing Charity Hospital of China Rehabilitation Research Center, Beijing, ChinaCenters for Cardiovascular Research and Inflammation, Translational, & Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USACenters for Cardiovascular Research and Inflammation, Translational, & Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USAMetabolic Disease Research & Thrombosis Research, Departments of Pharmacology, Microbiology and Immunology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USACenters for Cardiovascular Research and Inflammation, Translational, & Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USACenters for Cardiovascular Research and Inflammation, Translational, & Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USACenters for Cardiovascular Research and Inflammation, Translational, & Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USACenters for Cardiovascular Research and Inflammation, Translational, & Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USACenters for Cardiovascular Research and Inflammation, Translational, & Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USACenters for Cardiovascular Research and Inflammation, Translational, & Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USACenters for Cardiovascular Research and Inflammation, Translational, & Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USADepartment of Clinical Sciences, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USADepartment of Nephrology, Second Hospital of Shanxi Medical University, Shanxi Provincial People's Hospital, Taiyuan, Shanxi, ChinaHeart Center, St. Christopher’s Hospital for Children, Drexel University College of Medicine, Philadelphia, PA, USACenters for Cardiovascular Research and Inflammation, Translational, & Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USAMetabolic Disease Research & Thrombosis Research, Departments of Pharmacology, Microbiology and Immunology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USACenters for Cardiovascular Research and Inflammation, Translational, & Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USABackground. 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.http://dx.doi.org/10.1155/2021/6664453 |
| spellingShingle | Qian Yang Ruijing Zhang Peng Tang Yu Sun Candice Johnson Jason Saredy Susu Wu Jiwei Wang Yifan Lu Fatma Saaoud Ying Shao Charles Drummer Keman Xu Daohai Yu Rongshan Li Shuping Ge Xiaohua Jiang Hong Wang Xiaofeng Yang Ultrasound May Suppress Tumor Growth, Inhibit Inflammation, and Establish Tolerogenesis by Remodeling Innatome via Pathways of ROS, Immune Checkpoints, Cytokines, and Trained Immunity/Tolerance Journal of Immunology Research |
| title | Ultrasound May Suppress Tumor Growth, Inhibit Inflammation, and Establish Tolerogenesis by Remodeling Innatome via Pathways of ROS, Immune Checkpoints, Cytokines, and Trained Immunity/Tolerance |
| title_full | Ultrasound May Suppress Tumor Growth, Inhibit Inflammation, and Establish Tolerogenesis by Remodeling Innatome via Pathways of ROS, Immune Checkpoints, Cytokines, and Trained Immunity/Tolerance |
| title_fullStr | Ultrasound May Suppress Tumor Growth, Inhibit Inflammation, and Establish Tolerogenesis by Remodeling Innatome via Pathways of ROS, Immune Checkpoints, Cytokines, and Trained Immunity/Tolerance |
| title_full_unstemmed | Ultrasound May Suppress Tumor Growth, Inhibit Inflammation, and Establish Tolerogenesis by Remodeling Innatome via Pathways of ROS, Immune Checkpoints, Cytokines, and Trained Immunity/Tolerance |
| title_short | Ultrasound May Suppress Tumor Growth, Inhibit Inflammation, and Establish Tolerogenesis by Remodeling Innatome via Pathways of ROS, Immune Checkpoints, Cytokines, and Trained Immunity/Tolerance |
| title_sort | ultrasound may suppress tumor growth inhibit inflammation and establish tolerogenesis by remodeling innatome via pathways of ros immune checkpoints cytokines and trained immunity tolerance |
| url | http://dx.doi.org/10.1155/2021/6664453 |
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