{"doi":"10.4049/jimmunol.164.3.1588","title":"NF-κB Modulates TNF-α Production by Alveolar Macrophages in Asymptomatic HIV-Seropositive Individuals","abstract":"Local TNF-alpha production in different organs may affect HIV replication and pathogenesis. Alveolar macrophages (AMs) obtained by bronchoalveolar lavage from asymptomatic HIV-seropositive and HIV-seronegative individuals did not spontaneously release TNF-alpha, but LPS stimulation of these cells significantly increased TNF-alpha production. We tested whether NF-kappa B affects TNF-alpha production by AMs using N-tosyl-<cmd SC>l<cmd /SC> -phenylalanine chloromethylketone (TPCK) or N-benzoyl-<cmd SC>l<cmd /SC> -tyrosine ethyl ester (BTEE), which inhibit the degradation of I kappa B, or tricyclodecan-9-yl-xanthogenate-potassium (D609), which inhibits phospholipase C. Alveolar macrophages were exposed to LPS alone and with the chemical protease inhibitors TPCK, BTEE, and D609. NF-kappa B DNA binding induced by LPS treatment of AMs was inhibited by TPCK, BTEE, and D609. These agents also inhibited TNF-alpha mRNA and TNF-alpha protein production. After 24 h, the levels of TNF-alpha mRNA reached equilibrium, as assessed by RT-PCR. The levels of NF-kappa B mRNA remained constant under all conditions. The levels of I kappa B-alpha mRNA were similar after 30, 60, and 180 min, but the I kappa B-beta mRNA concentration was initially low and increased over time under all conditions. I kappa B-alpha and I kappa B-beta protein production was not affected by the chemical protease inhibitors. Our data show that TNF-alpha production by LPS-stimulated AMs from asymptomatic HIV-seropositive and -seronegative individuals is regulated via the phospholipase C pathway and by NF-kappa B DNA binding activity without obvious changes in I kappa B-alpha or I kappa B-beta protein concentrations.","journal":"The Journal of Immunology","year":2000,"id":750,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0449,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2000-02-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":7281,"name":"Suzanne M Melanson","orcid":null,"position":1,"is_corresponding":false},{"id":7282,"name":"Deborah J. Schiffer-Alberts","orcid":null,"position":2,"is_corresponding":false},{"id":148,"name":"John P. A. Ioannidis","orcid":"0000-0003-3118-6859","position":3,"is_corresponding":false},{"id":7283,"name":"Henry Koziel","orcid":null,"position":4,"is_corresponding":false},{"id":3970,"name":"Paul R. Skolnik","orcid":null,"position":5,"is_corresponding":false},{"id":7284,"name":"Jean‐Marie Mathys","orcid":null,"position":6,"is_corresponding":false},{"id":7285,"name":"Suzanne Melanson","orcid":null,"position":7,"is_corresponding":false},{"id":7280,"name":"Jean-Marie Mathys","orcid":null,"position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"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":[]}