{"doi":"10.4049/jimmunol.1901533","title":"Small-Molecule Inhibitor of 8-Oxoguanine DNA Glycosylase 1 Regulates Inflammatory Responses during <i>Pseudomonas aeruginosa</i> Infection","abstract":"Abstract The DNA repair enzyme 8-oxoguanine DNA glycosylase 1 (OGG1), which excises 8-oxo-7,8-dihydroguanine lesions induced in DNA by reactive oxygen species, has been linked to the pathogenesis of lung diseases associated with bacterial infections. A recently developed small molecule, SU0268, has demonstrated selective inhibition of OGG1 activity; however, its role in attenuating inflammatory responses has not been tested. In this study, we report that SU0268 has a favorable effect on bacterial infection both in mouse alveolar macrophages (MH-S cells) and in C57BL/6 wild-type mice by suppressing inflammatory responses, particularly promoting type I IFN responses. SU0268 inhibited proinflammatory responses during Pseudomonas aeruginosa (PA14) infection, which is mediated by the KRAS–ERK1–NF-κB signaling pathway. Furthermore, SU0268 induces the release of type I IFN by the mitochondrial DNA–cGAS–STING–IRF3–IFN-β axis, which decreases bacterial loads and halts disease progression. Collectively, our results demonstrate that the small-molecule inhibitor of OGG1 (SU0268) can attenuate excessive inflammation and improve mouse survival rates during PA14 infection. This strong anti-inflammatory feature may render the inhibitor as an alternative treatment for controlling severe inflammatory responses to bacterial infection.","journal":"The Journal of Immunology","year":2020,"id":94949,"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":37,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9524,"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":282909,"name":"Ping Lin","orcid":"0000-0002-4281-2440","position":1,"is_corresponding":false},{"id":282913,"name":"Qun Wu","orcid":"0000-0002-6301-5395","position":2,"is_corresponding":false},{"id":282911,"name":"Qinqin Pu","orcid":"0000-0001-8413-7802","position":3,"is_corresponding":false},{"id":337232,"name":"Chuan‐Min Zhou","orcid":"0000-0002-5975-4603","position":4,"is_corresponding":false},{"id":337233,"name":"Biao Wang","orcid":"0000-0001-7691-4368","position":5,"is_corresponding":false},{"id":282914,"name":"Pan Gao","orcid":"0000-0003-2276-2391","position":6,"is_corresponding":false},{"id":282912,"name":"Zhihan Wang","orcid":"0000-0002-3617-477X","position":7,"is_corresponding":false},{"id":472127,"name":"Ashley R Gao","orcid":"0000-0003-4477-6831","position":8,"is_corresponding":false},{"id":472634,"name":"M. Chris Overby","orcid":null,"position":9,"is_corresponding":false},{"id":472128,"name":"Jinliang Yang","orcid":"0000-0002-6152-6394","position":10,"is_corresponding":false},{"id":282919,"name":"Jianxin Jiang","orcid":"0000-0002-2945-1134","position":11,"is_corresponding":false},{"id":472129,"name":"David L. Wilson","orcid":"0000-0002-1922-427X","position":12,"is_corresponding":false},{"id":472635,"name":"Yu-ki Tahara","orcid":null,"position":13,"is_corresponding":false},{"id":329319,"name":"Eric T. Kool","orcid":"0000-0002-7310-2935","position":14,"is_corresponding":false},{"id":472130,"name":"Zhenwei Xia","orcid":"0000-0003-3811-4233","position":15,"is_corresponding":false},{"id":257445,"name":"Min Wu","orcid":"0000-0003-1205-982X","position":16,"is_corresponding":false},{"id":282910,"name":"Shugang Qin","orcid":"0000-0002-5771-6785","position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-18T22:33:00.770265Z","pmid":"32929043","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":[]}