{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T16:12:48Z","timestamp":1773763968845,"version":"3.50.1"},"reference-count":59,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2012,1,1]],"date-time":"2012-01-01T00:00:00Z","timestamp":1325376000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mol Pain"],"published-print":{"date-parts":[[2012,1,1]]},"abstract":"<jats:sec><jats:title>Background:<\/jats:title><jats:p> Proopiomelanocortin (POMC)-derived beta-endorphin<jats:sub>1-31<\/jats:sub> from immune cells can inhibit inflammatory pain. Here we investigated cytokine signaling pathways regulating POMC gene expression and beta-endorphin production in lymphocytes to augment such analgesic effects. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p> Interleukin-4 dose-dependently elevated POMC mRNA expression in na\u00efve lymph node-derived cells in vitro, as determined by real-time PCR. This effect was neutralized by janus kinase (JAK) inhibitors. Transfection of Signal Transducer and Activator of Transcription (STAT) 1\/3 but not of STAT6 decoy oligonucleotides abolished interleukin-4 induced POMC gene expression. STAT3 was phosphorylated in in vitro interleukin-4 stimulated lymphocytes and in lymph nodes draining inflamed paws in vivo. Cellular beta-endorphin increased after combined stimulation with interleukin-4 and concanavalin A. Consistently, in vivo reduction of inflammatory pain by passively transferred T cells improved significantly when donor cells were pretreated with interleukin-4 plus concanavalin A. This effect was blocked by naloxone-methiodide. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion:<\/jats:title><jats:p> Interleukin-4 can amplify endogenous opioid peptide expression mediated by JAK-STAT1\/3 activation in mitogen-activated lymphocytes. Transfer of these cells leads to inhibition of inflammatory pain via activation of peripheral opioid receptors. <\/jats:p><\/jats:sec>","DOI":"10.1186\/1744-8069-8-83","type":"journal-article","created":{"date-parts":[[2012,11,13]],"date-time":"2012-11-13T12:52:34Z","timestamp":1352811154000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":28,"title":["JAK-STAT1\/3-Induced Expression of Signal Sequence-Encoding Proopiomelanocortin mRNA in Lymphocytes Reduces Inflammatory Pain in Rats"],"prefix":"10.1177","volume":"8","author":[{"given":"Melanie","family":"Busch-Dienstfertig","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Charit\u00e9 Campus Benjamin Franklin, Freie Universit\u00e4t Berlin, Hindenburgdamm 30, 12200, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominika","family":"Labuz","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Charit\u00e9 Campus Benjamin Franklin, Freie Universit\u00e4t Berlin, Hindenburgdamm 30, 12200, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theresa","family":"Wolfram","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Charit\u00e9 Campus Benjamin Franklin, Freie Universit\u00e4t Berlin, Hindenburgdamm 30, 12200, Berlin, Germany"},{"name":"current address: MorphoSys AG, Lena-Christ-Str. 48, 82152, Martinsried\/Planegg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole N","family":"Vogel","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Charit\u00e9 Campus Benjamin Franklin, Freie Universit\u00e4t Berlin, Hindenburgdamm 30, 12200, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Stein","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Charit\u00e9 Campus Benjamin Franklin, Freie Universit\u00e4t Berlin, Hindenburgdamm 30, 12200, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2012,1,1]]},"reference":[{"key":"bibr1-1744-8069-8-83","first-page":"10","volume":"61","author":"Paulozzi LJ","year":"2012","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"bibr2-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.36076\/ppj.2011\/14\/249"},{"key":"bibr3-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(93)91471-W"},{"key":"bibr4-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1097\/01.ajp.0000210954.93878.0d"},{"key":"bibr5-1744-8069-8-83","doi-asserted-by":"crossref","unstructured":"Schreiter A, Gore C, Labuz D, Fournie-Zaluski M-C, Roques BP, Stein C, Machelska M: Pain inhibition by blocking leukocytic and neuronal opioid peptidases in peripheral inflamed tissue FASEB J 2012. published ahead of print August 24 2012.","DOI":"10.1096\/fj.12-208678"},{"key":"bibr6-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.10-04-01292.1990"},{"key":"bibr7-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-6077fje"},{"key":"bibr8-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1038\/nm908"},{"key":"bibr9-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.10.4219"},{"key":"bibr10-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(92)90509-Z"},{"key":"bibr11-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1213\/01.ANE.0000099369.23397.D7"},{"key":"bibr12-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.1999.00612.x"},{"key":"bibr13-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1991.tb00577.x"},{"key":"bibr14-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1084\/jem.163.6.1589"},{"key":"bibr15-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.2108\/zsj.20.1183"},{"key":"bibr16-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119506"},{"key":"bibr17-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)81472-2"},{"key":"bibr18-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.20.7261"},{"key":"bibr19-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1210\/mend-2-9-862"},{"key":"bibr20-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1210\/endo.133.5.8404638"},{"key":"bibr21-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2006.11.033"},{"key":"bibr22-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(97)00081-7"},{"key":"bibr23-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1016\/0889-1591(91)90027-8"},{"key":"bibr24-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00282-3"},{"key":"bibr25-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1101\/gad.10.10.1284"},{"key":"bibr26-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(04)00303-5"},{"key":"bibr27-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1210\/mend.16.7.0863"},{"key":"bibr28-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M804965200"},{"key":"bibr29-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.72.9.3590"},{"key":"bibr30-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1016\/0300-9084(94)90156-2"},{"key":"bibr31-1744-8069-8-83","first-page":"1021","volume":"115","author":"Scholzen TE","year":"2000","journal-title":"J"},{"key":"bibr32-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1210\/endo.139.5.6005"},{"key":"bibr33-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1220033"},{"key":"bibr34-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(97)00113-6"},{"key":"bibr35-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.1.51.pe55"},{"key":"bibr36-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M107543200"},{"key":"bibr37-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00613-07"},{"key":"bibr38-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1210\/en.2002-220323"},{"key":"bibr39-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0906583"},{"key":"bibr40-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/25.11.2062"},{"key":"bibr41-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.16.10723"},{"key":"bibr42-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90356-5"},{"key":"bibr43-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(99)00268-7"},{"key":"bibr44-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0306209"},{"key":"bibr45-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2005.09.019"},{"key":"bibr46-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-1287"},{"key":"bibr47-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.102.038703"},{"key":"bibr48-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702266"},{"key":"bibr49-1744-8069-8-83","first-page":"1065","volume":"118","author":"Z\u00f6llner C","year":"2008","journal-title":"J Clin Invest"},{"key":"bibr50-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.01.045"},{"key":"bibr51-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-5-72"},{"key":"bibr52-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(83)90201-4"},{"key":"bibr53-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-4280"},{"key":"bibr54-1744-8069-8-83","doi-asserted-by":"crossref","first-page":"22","DOI":"10.4049\/jimmunol.159.1.22","volume":"159","author":"Elder RT","year":"1997","journal-title":"J Immunol"},{"key":"bibr55-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1021\/jm0502034"},{"key":"bibr56-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0482fje"},{"key":"bibr57-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2004.03459.x"},{"key":"bibr58-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1038\/227680a0"},{"key":"bibr59-1744-8069-8-83","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.15.5935"}],"container-title":["Molecular Pain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1186\/1744-8069-8-83","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1186\/1744-8069-8-83","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1186\/1744-8069-8-83","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T15:22:55Z","timestamp":1741620175000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1186\/1744-8069-8-83"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,1,1]]},"references-count":59,"alternative-id":["10.1186\/1744-8069-8-83"],"URL":"https:\/\/doi.org\/10.1186\/1744-8069-8-83","relation":{},"ISSN":["1744-8069","1744-8069"],"issn-type":[{"value":"1744-8069","type":"print"},{"value":"1744-8069","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,1,1]]},"article-number":"1744-8069-8-83"}}