Treatment of inflamed pancreas with enkephalin encoding HSV-1 recombinant vector reduces inflammatory damage and behavioral sequelae.
This study assessed the efficacy of pancreatic surface delivered enkephalin (ENK)-encoding herpes simplex virus type 1 (HSV-1) on spontaneous behaviors and spinal cord and pancreatic enkephalin expression in an experimental pancreatitis model. Replication-defective HSV-1 with proenkephalin complementary DNA (cDNA) (HSV-ENK) or control beta-galactosidase cDNA (HSV-beta-gal), or media vehicle (Veh) was applied to the pancreatic surface of rats with dibutyltin dichloride (DBTC)-induced pancreatitis. Spontaneous exploratory behavioral activity was monitored on days 0 and 6 post DBTC and vector treatments. The pancreas, thoracic dorsal root ganglia (DRG, T9-10), and spinal cord (T9-10) were immunostained for met-enkephalin (met-ENK), beta-gal, and HSV-1 proteins. Spinal cord was also immunostained for c-Fos, and pancreas was stained for the inflammatory marker regulated on activation, normal T-cells expressed and secreted (RANTES), mu-opioid receptor, and hemotoxylin/eosin. On day 6, compared to pancreatitis and vector controls, the DBTC/HSV-ENK treated rats had significantly improved spontaneous exploratory activities, increased met-ENK staining in the pancreas and spinal cord, and normalized c-Fos staining in the dorsal horn. Histopathology of pancreas in DBTC/HSV-ENK treated rats showed preservation of acinar cells and cytoarchitecture with minimal inflammatory cell infiltrates, compared to severe inflammation and acinar cell loss seen in DBTC/HSV-beta-gal and DBTC/Veh treated rats. Targeted transgene delivery and met-ENK expression successfully produced decreased inflammation in experimental pancreatitis.
Lu
Ying
Y
Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, Texas, USA.
McNearney
Terry A
TA
Lin
Weidong
W
Wilson
Steven P
SP
Yeomans
David C
DC
Westlund
Karin N
KN
D000818:Animals; D001522:Behavior, Animal; D004745:Enkephalins / Q000235:genetics*; D015316:Genetic Therapy; D005822:Genetic Vectors; D018259:Herpesvirus 1, Human / Q000235:genetics*; D007150:Immunohistochemistry; D007249:Inflammation / Q000628:therapy*; D010179:Pancreas / Q000378:metabolism; D010195:Pancreatitis / Q000628:therapy*; D051381:Rats; D013116:Spinal Cord / Q000378:metabolism
D004745:Enkephalins