{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T10:18:45Z","timestamp":1786702725638,"version":"build-2736575974"},"reference-count":100,"publisher":"Bioscientifica","issue":"1","content-domain":{"domain":["jme.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:p>\n                    Type 1 diabetes is caused by an autoimmune assault that induces progressive beta-cell dysfunction and dead. Pro-inflammatory cytokines, such as interleukin 1 beta (IL1B), tumor necrosis factor (TNF) and interferon gamma (IFNG) contribute for beta-cell death, which involves the activation of the nuclear factor kappa B (NF\u03baB) and c- Jun N-terminal kinase (JNK). Prolactin (PRL), a physiological mediator for beta-cell proliferation, was shown to protect beta cells against cytokines pro-apoptotic effects. We presently investigated the mechanisms involved in the protective effects of prolactin against cytokine-induced beta-cell death. The findings obtained indicate that STAT3 activation is involved in the anti-apoptotic role of PRL in rat beta cells. PRL prevents the activation of JNK via AKT and promotes a shift from expression of pro- to anti-apoptotic proteins downstream of the JNK cascade. Furthermore, PRL partially prevents the activation of NF\u03baB and the transcription of its target genes\n                    <jats:italic>IkBa<\/jats:italic>\n                    ,\n                    <jats:italic>Fas<\/jats:italic>\n                    ,\n                    <jats:italic>Mcp1<\/jats:italic>\n                    , A20 and\n                    <jats:italic>Cxcl10<\/jats:italic>\n                    and also decreases NO production. On the other hand, the pro-survival effects of PRL do not involve modulation of cytokine-induced endoplasmic reticulum stress. These results suggest that the beneficial effects of PRL in beta cells involve augmentation of anti-apoptotic mechanisms and, at the same time, reduction of pro-apoptotic effectors, rendering beta cells better prepared to deal with inflammatory insults. The better understanding of the pro-survival mechanisms modulated by PRL in beta cells can provide tools to prevent cell demise during an autoimmune attack or following islet transplantation.\n                  <\/jats:p>","DOI":"10.1530\/jme-16-0257","type":"journal-article","created":{"date-parts":[[2018,4,9]],"date-time":"2018-04-09T12:10:16Z","timestamp":1523275816000},"page":"25-36","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-6","source":"Crossref","is-referenced-by-count":17,"title":["Prolactin protects against cytokine-induced beta-cell death by NF\u03baB and JNK inhibition"],"prefix":"10.1530","volume":"61","author":[{"given":"Tarlliza R","family":"Nardelli","sequence":"first","affiliation":[{"name":"1Department of Structural and Functional Biology, Laboratory of Endocrine Pancreas and Metabolism, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emerielle C","family":"Vanzela","sequence":"additional","affiliation":[{"name":"1Department of Structural and Functional Biology, Laboratory of Endocrine Pancreas and Metabolism, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keli C","family":"Benedicto","sequence":"additional","affiliation":[{"name":"1Department of Structural and Functional Biology, Laboratory of Endocrine Pancreas and Metabolism, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flora","family":"Brozzi","sequence":"additional","affiliation":[{"name":"2ULB Center for Diabetes Research, Medical Faculty, Universit\u00e9 Libre de Bruxelles (ULB), Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Fujita","sequence":"additional","affiliation":[{"name":"3Department of Computer Science, Institute of Mathematics and Statistics, University of S\u00e3o Paulo (USP), S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra K","family":"Cardozo","sequence":"additional","affiliation":[{"name":"2ULB Center for Diabetes Research, Medical Faculty, Universit\u00e9 Libre de Bruxelles (ULB), Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e9cio L","family":"Eizirik","sequence":"additional","affiliation":[{"name":"2ULB Center for Diabetes Research, Medical Faculty, Universit\u00e9 Libre de Bruxelles (ULB), Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio C","family":"Boschero","sequence":"additional","affiliation":[{"name":"1Department of Structural and Functional Biology, Laboratory of Endocrine Pancreas and Metabolism, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"Ortis","sequence":"additional","affiliation":[{"name":"4Department of Cell and Developmental Biology, Institute of Biomedical Science (ICB), University of S\u00e3o Paulo (USP), S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"ref281","doi-asserted-by":"crossref","first-page":"e3030","DOI":"10.1371\/journal.pone.0003030","article-title":"JunB inhibits ER stress and apoptosis in pancreatic beta cells","volume":"3","year":"2008","journal-title":"PLoS ONE"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1210\/endo.130.1.1370150","article-title":"Establishment of 2-mercaptoethanol-dependent differentiated insulin-secreting cell lines","volume":"130","year":"1992","journal-title":"Endocrinology"},{"key":"ref111","doi-asserted-by":"crossref","first-page":"48879","DOI":"10.1074\/jbc.M108658200","article-title":"A 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