{"doi":"10.17615/e6d1-j535","title":"Positive and negative regulation of NF-κB by COX-2. Roles of different prostaglandins","abstract":"The prostaglandin H synthases (PGHS) catalyze the conversion of arachidonic acid to prostaglandin H2, the committed step in prostanoid synthesis. Two forms of PGHS exist, PGHS-1 (COX-1) and PGHS-2 (COX-2). The gene encoding the latter form is known to be inducible by a number of stimuli including several inflammatory mediators. Recent evidence indicates that the inducible cyclooxygenase may have both pro- and anti-inflammatory properties through the generation of different prostaglandins. Previous reports indicate that the transcription factor NF-κB can function upstream of COX-2 to control transcription of this gene and that the cyclopentenone prostaglandins can inhibit NF-κB activation via the inhibition of the IκB kinase. Thus, it is suggested that cyclopentenones feed back to inhibit continued nuclear accumulation of NF-κB. In this report we demonstrate COX-2 expression inhibits nuclear translocation of NF-κB, and we confirm that the cyclopentenone prostaglandins inhibit NF-κB. In addition, we show that prostaglandin E2 and its analogs promote the inherent transcriptional activity of the p65/RelA subunit of NF-κB in a manner independent of induced nuclear accumulation. Consistent with this evidence, prostaglandin E2 strongly synergizes with the inflammatory cytokine tumor necrosis factor-α to promote NF-κB-dependent transcription and gene expression. The data provide a molecular rationale to explain both the pro-and anti-inflammatory nature of COX-2.","journal":"UNC Libraries","year":2022,"id":294730,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9462,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":450372,"name":"A.S. Baldwin","orcid":null,"position":1,"is_corresponding":false},{"id":980456,"name":"B. Poligone","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T00:31:01.450041Z","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":[]}