title: B Lymphocytes Express Pomc mRNA, Processing Enzymes and β-Endorphin in Painful Inflammation.
abstract: Immune cell-derived beta-endorphin (END) and other opioid peptides elicit potent and clinically relevant inhibition of pain (analgesia) in inflamed tissue by activation of peripheral opioid receptors. Pro-opiomelanocortin (POMC) is the polypeptide precursor of END and is processed by prohormone convertases (PCs). This study aims to decipher the processing of POMC in lymphocyte subsets in a rat model of unilateral painful hindpaw inflammation. Lymphocytes, isolated from popliteal lymph nodes, were separated into B-cells, T-cells, T-helper cells and cytotoxic T-cells using magnetic cell sorting, and were examined by polymerase chain reaction, immunofluorescence and radioimmunoassay. At 2 h of inflammation, POMC exon 2-3 mRNA was mostly expressed in B- but not in T-cells. Prohormone convertase 1 (PC1) mRNA and protein were upregulated in B-cells and T-helper cells. Prohormone convertase 2 (PC2) was expressed in T- and B-cells, both in inflamed and non-inflamed lymph nodes. END was expressed in B- but not in T-cells. We conclude that POMC, its processing enzymes and END are predominantly expressed in B-lymphocytes at 2 h of paw inflammation.
authors.affiliation: Klinik für Anästhesiologie und operative Intensivmedizin, Freie Universität Berlin, Charité Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany.
authors.forename: Santhosh Chandar
authors.initials: SC
authors.lastname: Maddila
authors.affiliation: Klinik für Anästhesiologie und operative Intensivmedizin, Freie Universität Berlin, Charité Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Busch-Dienstfertig
authors.affiliation: Klinik für Anästhesiologie und operative Intensivmedizin, Freie Universität Berlin, Charité Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany. christoph.stein@charite.de.
authors.forename: Christoph
authors.identifier: 0000-0001-5240-6836
authors.initials: C
authors.lastname: Stein
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology / Q000378:metabolism*; D015870:Gene Expression; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D008297:Male; D010146:Pain / Q000235:genetics / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis* / Q000235:genetics; D045664:Proprotein Convertase 1 / Q000096:biosynthesis / Q000235:genetics; D045706:Proprotein Convertase 2 / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012697:Serine Endopeptidases / Q000096:biosynthesis* / Q000235:genetics; D001615:beta-Endorphin / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin; D012697:Serine Endopeptidases; D045664:Proprotein Convertase 1; D045706:Proprotein Convertase 2
keywords: Endorphin; Inflammation; Lymphocytes; Opioid; Pain; Prohormone convertase; Proopiomelanocortin