{"doi":"10.17615/prmr-yn61","title":"Signaling pathways mediating β3-adrenergic receptor-induced production of interleukin-6 in adipocytes","abstract":"The β3-adrenergic receptor (β3AR) is an essential regulator of metabolic and endocrine functions. A major cellular and clinically significant consequence of β3AR activation is the substantial elevation in interleukin-6 (IL-6) levels. Although the β3AR-dependent regulation of IL-6 expression is well established, the cellular pathways underlying this regulation have not been characterized. Using a novel method of homogenous reporters, we assessed the pattern of activation of 43 transcription factors in response to the specific β3AR agonist {\"type\":\"entrez-nucleotide\",\"attrs\":{\"text\":\"CL316243\",\"term_id\":\"44896132\",\"term_text\":\"CL316243\"}}CL316243 in adipocytes, cells that exhibit the highest expression of β3ARs. We observed a unique and robust activation of the CRE-response element, suggesting that IL-6 transcription is regulated via the Gs-protein/cAMP/protein kinase A (PKA) but not nuclear factor kappa B (NF-κB) pathway. However, pretreatment of adipocytes with pharmacologic inhibitors of PKA pathway failed to block β3AR-mediated IL-6 up-regulation. Additionally, stimulation of adipocytes with the exchange protein directly activated by cAMP (Epac) agonist did not induce IL-6 expression. Instead, the β3AR-mediated transcription of IL-6 required activation of both the p38 and PKC pathways. Western blot analysis further showed that transcription factors CREB and ATF-2 but not ATF-1 were activated in a p38- and PKC-dependent manner. Collectively, our results suggest that while stimulation of the β3AR leads to a specific activation of CRE-dependent transcription, there are several independent cellular pathways that converge at the level of CRE-response element activation, and in the case of IL-6 this activation is mediated by p38 and PKC but not PKA pathways.","journal":"UNC Libraries","year":2020,"id":137859,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9544,"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":413987,"name":"Andrea G. Nackley","orcid":"0000-0003-3688-2271","position":1,"is_corresponding":false},{"id":599179,"name":"S. G. Romanov","orcid":null,"position":2,"is_corresponding":false},{"id":393555,"name":"Luda Diatchenko","orcid":"0000-0002-1350-6727","position":3,"is_corresponding":false},{"id":598548,"name":"Sergei S. Makarov","orcid":"0000-0003-1314-6909","position":4,"is_corresponding":false},{"id":595577,"name":"Patrick M. Flood","orcid":null,"position":5,"is_corresponding":false},{"id":598549,"name":"Alexander V. Medvedev","orcid":"0000-0001-6983-1687","position":6,"is_corresponding":false},{"id":130820,"name":"William Maixner","orcid":null,"position":7,"is_corresponding":false},{"id":547081,"name":"Kai Soo Tan","orcid":"0000-0002-9865-9828","position":8,"is_corresponding":false},{"id":599180,"name":"Maria Gambarian","orcid":null,"position":9,"is_corresponding":false},{"id":505216,"name":"Inna E. Tchivileva","orcid":"0000-0003-0968-0594","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:16:59.449905Z","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":[]}