Lymphocytes upregulate signal sequence-encoding proopiomelanocortin mRNA and beta-endorphin during painful inflammation in vivo.
Proopiomelanocortin (POMC)-derived beta-endorphin1-31 (END) released from immune cells inhibits inflammatory pain. We examined the expression of END and POMC mRNA encoding the signal sequence required for entry of the nascent polypeptide into the regulated secretory pathway in lymphocytes of rats with inflamed hindpaws. Within 12 h of inflammation, END increased in popliteal lymph nodes and at 96 h the intraplantar neutralization of END exacerbated pain. Lymphocytes expressed POMC, END, and full-length POMC mRNA. Semi-nested PCR revealed 8-fold increased exon 2-3 spanning POMC mRNA. Thus, painful inflammation enhances signal sequence-encoding lymphocytic POMC mRNA needed for regulated secretion of functionally active END.
Sitte
Nicolle
N
Department of Anesthesiology and Critical Care Medicine, Charité University Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany.
Busch
Melanie
M
Mousa
Shaaban A
SA
Labuz
Dominika
D
Rittner
Heike
H
Gore
Carmen
C
Krause
Hans
H
Stein
Christoph
C
Schäfer
Michael
M
D000818:Animals; D005434:Flow Cytometry / Q000379:methods; D005620:Freund's Adjuvant; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D007249:Inflammation / Q000139:chemically induced / Q000150:complications / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D010146:Pain / Q000209:etiology / Q000473:pathology*; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism*; D021382:Protein Sorting Signals; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D001615:beta-Endorphin / Q000378:metabolism*
D021382:Protein Sorting Signals; D012333:RNA, Messenger; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin; D005620:Freund's Adjuvant