Ultrasound May Suppress Tumor Growth, Inhibit Inflammation, and Establish Tolerogenesis by Remodeling Innatome via Pathways of ROS, Immune Checkpoints, Cytokines, and Trained Immunity/Tolerance.
Adaptive Immunity
Cells, Cultured
Cytokines
/ metabolism
Gene Expression Profiling
Humans
Hyperthermia, Induced
/ methods
Immune Checkpoint Proteins
/ genetics
Immunity, Innate
Immunomodulation
/ radiation effects
Models, Biological
Neoplasms
/ etiology
Reactive Oxygen Species
/ metabolism
Signal Transduction
/ radiation effects
Tumor Escape
/ immunology
Ultrasonic Waves
Journal
Journal of immunology research
ISSN: 2314-7156
Titre abrégé: J Immunol Res
Pays: Egypt
ID NLM: 101627166
Informations de publication
Date de publication:
2021
2021
Historique:
received:
14
10
2020
revised:
27
11
2020
accepted:
16
12
2020
entrez:
25
2
2021
pubmed:
26
2
2021
medline:
15
10
2021
Statut:
epublish
Résumé
The immune mechanisms underlying low-intensity ultrasound- (LIUS-) mediated suppression of inflammation and tumorigenesis remain poorly determined. 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. 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. 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.
Sections du résumé
BACKGROUND
BACKGROUND
The immune mechanisms underlying low-intensity ultrasound- (LIUS-) mediated suppression of inflammation and tumorigenesis remain poorly determined.
METHODS
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
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
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.
Identifiants
pubmed: 33628851
doi: 10.1155/2021/6664453
pmc: PMC7889351
doi:
Substances chimiques
Cytokines
0
Immune Checkpoint Proteins
0
Reactive Oxygen Species
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
6664453Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL138749
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL130233
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL131460
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK104116
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL147565
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK113775
Pays : United States
Informations de copyright
Copyright © 2021 Qian Yang et al.
Déclaration de conflit d'intérêts
The authors have no competing interests to disclose.
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