{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T13:55:01Z","timestamp":1753883701055,"version":"3.41.2"},"reference-count":31,"publisher":"The Endocrine Society","issue":"11","license":[{"start":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T00:00:00Z","timestamp":1727913600000},"content-version":"vor","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Schweizerische Gesellschaft f\u00fcr Endokrinologie und Diabetologie SGED"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Prohormone convertase 1\/3 (PC1\/3) is an endopeptidase required for the processing of neuropeptide and endocrine peptide precursors; it is expressed in neuroendocrine tissues as well as in immune cells. In response to endotoxemia, global PC1\/3 knockout mice mount a cytokine storm and die rapidly. Further, immune cells isolated from these mice have a pro-inflammatory signature, suggesting that PC1\/3 activates an unknown anti-inflammatory peptide precursor in immune cells. Here, we tested this hypothesis using tissue-specific PC1\/3 ablation models. Knocking out PC1\/3 in the myeloid or the hematopoietic compartment did not induce any phenotype. In contrast, proopiomelanocortin (POMC)-specific PC1\/3 knockout mice phenocopied global PC1\/3 knockout mice, including an enlarged spleen size and a hyperinflammatory sepsis phenotype in response to mild endotoxemia. This phenotype was prevented by steroid therapy and mimicked by blocking corticoid receptors in wild-type mice. Thus, our data suggest that sepsis hypersensitivity in PC1\/3 deficiency is uncoupled from immune cell intrinsic PC1\/3 expression and is driven by a lack of anti-inflammatory glucocorticoids due to an impairment in the hypothalamic-pituitary-adrenal axis.<\/jats:p>","DOI":"10.1210\/jendso\/bvae171","type":"journal-article","created":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T04:27:21Z","timestamp":1727929641000},"source":"Crossref","is-referenced-by-count":0,"title":["Ablation of PC1\/3 in POMC-Expressing Tissues but Not in Immune Cells Induces Sepsis Hypersensitivity"],"prefix":"10.1210","volume":"8","author":[{"given":"Jana","family":"Moeller","sequence":"first","affiliation":[{"name":"Clinic of Endocrinology, Diabetes and Metabolism, University Hospital Basel , 4031 Basel ,","place":["Switzerland"]},{"name":"Department of Biomedicine, University of Basel , 4031 Basel ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3348-4657","authenticated-orcid":false,"given":"Daniel T","family":"Meier","sequence":"additional","affiliation":[{"name":"Clinic of Endocrinology, Diabetes and Metabolism, University Hospital Basel , 4031 Basel ,","place":["Switzerland"]},{"name":"Department of Biomedicine, University of Basel , 4031 Basel ,","place":["Switzerland"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2024,10,3]]},"reference":[{"issue":"5703","key":"2024102913421339300_bvae171-B1","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/278423a0","article-title":"Nucleotide sequence of cloned cDNA for bovine corticotropin-beta-lipotropin precursor","volume":"278","author":"Nakanishi","year":"1979","journal-title":"Nature"},{"issue":"1","key":"2024102913421339300_bvae171-B2","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1007\/s11481-016-9715-4","article-title":"B lymphocytes express pomc mRNA, processing enzymes and beta-endorphin in painful inflammation","volume":"12","author":"Maddila","year":"2017","journal-title":"J Neuroimmune Pharmacol"},{"issue":"4","key":"2024102913421339300_bvae171-B3","doi-asserted-by":"crossref","first-page":"e61557","DOI":"10.1371\/journal.pone.0061557","article-title":"Proprotein convertase 1\/3 (PC1\/3) in the rat alveolar macrophage cell line NR8383: localization, trafficking and effects on cytokine secretion","volume":"8","author":"Gagnon","year":"2013","journal-title":"PLoS One"},{"issue":"4","key":"2024102913421339300_bvae171-B4","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/0143-4179(94)90004-3","article-title":"Prohormone convertases PC2 and PC3 in rat neutrophils and macrophages. 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