{"doi":"10.17615/bfx9-j602","title":"EGFR Regulates the Expression of Keratinocyte-Derived Granulocyte/Macrophage Colony-Stimulating Factor In Vitro and In Vivo","abstract":"Recent advances in the knowledge of the EGFR pathway have revealed its contribution to distinct immune/ inflammatory functions of the epidermis. The purpose of our study was to evaluate the role of EGFR in the regulation of keratinocyte GM-CSF expression. In cultured human keratinocytes, proinflammatory cytokines synergized with TGF-α to induce GM-CSF expression. Accordingly, high epidermal levels of EGFR activation are associated with enhanced expression of GM-CSF in lesional skin of patients with psoriasis or allergic contact dermatitis. In cultured keratinocytes, pharmacological inhibition of EGFR activity reduced GM-CSF promoter transactivation, whereas genetic inhibition of AP-1 reduced expression of GM-CSF. Furthermore, EGFR activation enhanced TNF-α-induced c-Jun phosphorylation and DNA binding, whereas c-Jun silencing reduced GM-CSF expression. Using two different mouse models, we showed that the lack of a functional EGFR pathway was associated with reduced cytokine-induced phosphorylation of ERK1/2, JNK1/2, c-Jun and reduced keratinocyte-derived GM-CSF expression both in vitro and in vivo. Finally, the analysis of GM-CSF expression in the skin of cancer patients treated with anti EGFR drugs showed an association between ERK activity, c-Jun phosphorylation, and epidermal GM-CSF expression. These data demonstrate that the EGFR pathway is critical for the upregulation of keratinocyte GM-CSF expression under conditions of cytokine stimulation.","journal":"UNC Libraries","year":2021,"id":230363,"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":0.9602,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":836776,"name":"Francesca Mascia","orcid":null,"position":1,"is_corresponding":false},{"id":836110,"name":"Paolo Amerio","orcid":"0000-0003-1589-9672","position":2,"is_corresponding":false},{"id":836777,"name":"Saveria Pastore","orcid":null,"position":3,"is_corresponding":false},{"id":468779,"name":"Chinmayi Chandrasekhara","orcid":null,"position":4,"is_corresponding":false},{"id":93161,"name":"V. Mariani","orcid":"0000-0001-7108-8116","position":5,"is_corresponding":false},{"id":623636,"name":"Christophe Cataisson","orcid":"0000-0003-2600-1573","position":6,"is_corresponding":false},{"id":623637,"name":"Stuart H. Yuspa","orcid":"0000-0003-4785-337X","position":7,"is_corresponding":false},{"id":262707,"name":"David W. Threadgill","orcid":"0000-0003-3538-1635","position":8,"is_corresponding":false},{"id":713705,"name":"Gema Souto Adeva","orcid":null,"position":9,"is_corresponding":false},{"id":532346,"name":"Tang-Cheng Lee","orcid":null,"position":10,"is_corresponding":false},{"id":271979,"name":"Giampiero Girolomoni","orcid":"0000-0001-8548-0493","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:55:05.844766Z","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":[]}