{"doi":"10.4049/jimmunol.1900949","title":"Glycyrrhizin Protects γ-Irradiated Mice from Gut Bacteria–Associated Infectious Complications by Improving <i>miR-222</i>–Associated <i>Gas5</i> RNA Reduction in Macrophages of the Bacterial Translocation Site","abstract":"Abstract Gut bacteria–associated sepsis is a serious concern in patients with gastrointestinal acute radiation syndrome (GIARS). In our previous studies, gut bacteria–associated sepsis caused high mortality rates in mice exposed to 6–9 Gy of γ-rays. IL-12+CD38+ iNOS+ Mϕ (M1Mϕ) located in the bacterial translocation site (mesenteric lymph nodes [MLNs]) of unirradiated mice were characterized as host defense antibacterial effector cells. However, cells isolated from the MLNs of GIARS mice were mostly CCL1+IL-10+LIGHT+miR-27a+ Mϕ (M2bMϕ, inhibitor cells for the M1Mϕ polarization). Reduced long noncoding RNA Gas5 and increased miR-222 expression in MLN-Mϕ influenced by the irradiation were shown to be associated with M2bMϕ polarization. In this study, the mortality of mice exposed to 7 Gy of γ-rays (7 Gy GIARS mice) was completely controlled after the administration of glycyrrhizin (GL), a major active ingredient in licorice root (Glycyrrhiza glabra). Bacterial translocation and subsequent sepsis were minimal in 7 Gy GIARS mice treated with GL. Increased Gas5 RNA level and decreased miR-222 expression were shown in MLN-Mϕ isolated from 7 Gy GIARS mice treated with GL, and these macrophages did not display any properties of M2bMϕ. These results indicate that gut bacteria–associated sepsis in 7 Gy GIARS mice was controlled by the GL through the inhibition of M2bMϕ polarization at the bacteria translocation site. Expression of Ccl1, a gene required for M2bMϕ survival, is silenced in the MLNs of 7 Gy GIARS mice because of Gas5 RNA, which is increased in these cells after the suppression of miR-222 (a Gas5 RNA expression inhibitor) by the GL.","journal":"The Journal of Immunology","year":2020,"id":80851,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9517,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":419349,"name":"Bradford D. Loucas","orcid":null,"position":1,"is_corresponding":false},{"id":290849,"name":"Sumihiro Suzuki","orcid":"0000-0002-6408-9580","position":2,"is_corresponding":false},{"id":419350,"name":"Makiko Kobayashi","orcid":null,"position":3,"is_corresponding":false},{"id":419351,"name":"Fujio Suzuki","orcid":null,"position":4,"is_corresponding":false},{"id":418571,"name":"Ichiaki Ito","orcid":"0000-0002-3425-0070","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-18T21:51:58.988919Z","pmid":"31941655","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}