{"doi":"10.1083/jcb.202206095","title":"TIMP-1 is a novel ligand of Amyloid Precursor Protein and triggers a proinflammatory phenotype in human monocytes","abstract":"The emerging cytokine tissue inhibitor of metalloproteinases-1 (TIMP-1) correlates with the progression of inflammatory diseases, including cancer. However, the effects of TIMP-1 on immune cell activation and underlying molecular mechanisms are largely unknown. Unbiased ligand-receptor-capture-screening revealed TIMP-1-interaction with Amyloid Precursor Protein (APP) family members, namely APP and Amyloid Precursor-like Protein-2 (APLP2), which was confirmed by pull-down assays and confocal microscopy. We found that TIMP-1 triggered glucose uptake and proinflammatory cytokine expression in human monocytes. In cancer patients, TIMP-1 expression positively correlated with proinflammatory cytokine expression and processes associated with monocyte activation. In pancreatic cancer, TIMP-1 plasma levels correlated with the monocyte activation marker sCD163, and the combined use of both clinically accessible plasma proteins served as a powerful prognostic indicator. Mechanistically, TIMP-1 triggered monocyte activation by its C-terminal domain and via APP as demonstrated by in vitro interference, in silico docking, and the employment of recombinant TIMP-1 variants. Identification of TIMP-1 as a trigger of monocyte activation opens new therapeutic perspectives for inflammatory diseases.","journal":"The Journal of Cell Biology","year":2023,"id":331847,"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":26,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9627,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":711641,"name":"Benjamin Schoeps","orcid":"0000-0003-3934-0849","position":1,"is_corresponding":false},{"id":711647,"name":"Daniel Häußler","orcid":"0000-0003-0658-3262","position":2,"is_corresponding":false},{"id":1057297,"name":"Julian Frädrich","orcid":"0000-0002-0585-537X","position":3,"is_corresponding":false},{"id":374626,"name":"Felix Bayerl","orcid":"0000-0002-4737-1808","position":4,"is_corresponding":false},{"id":711645,"name":"Jan P. Böttcher","orcid":"0000-0002-8163-8107","position":5,"is_corresponding":false},{"id":561,"name":"Percy A. Knolle","orcid":"0000-0003-2983-0414","position":6,"is_corresponding":false},{"id":136209,"name":"Simone Heisz","orcid":"0000-0002-7596-909X","position":7,"is_corresponding":false},{"id":1057298,"name":"Olga Prokopchuk","orcid":"0000-0002-0697-512X","position":8,"is_corresponding":false},{"id":89433,"name":"Hans Hauner","orcid":"0000-0002-1682-5088","position":9,"is_corresponding":false},{"id":1057299,"name":"Enkhtsetseg Munkhbaatar","orcid":"0000-0002-2427-5952","position":10,"is_corresponding":false},{"id":55125,"name":"İhsan Ekin Demir","orcid":"0000-0001-8241-1871","position":11,"is_corresponding":false},{"id":711646,"name":"Chris D. Hermann","orcid":"0000-0002-2269-5259","position":12,"is_corresponding":false},{"id":711648,"name":"Achim Krüger","orcid":"0000-0002-1517-9256","position":13,"is_corresponding":false},{"id":711642,"name":"Celina Eckfeld","orcid":"0000-0002-2807-5368","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-19T01:09:25.015646Z","pmid":"36629908","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":[]}