Details

Autor(en) / Beteiligte

• Lu, Ying
• McNearney, Terry A
• Lin, Weidong
• Wilson, Steven P
• Yeomans, David C
• Westlund, Karin N

Titel

Treatment of Inflamed Pancreas with Enkephalin Encoding HSV-1 Recombinant Vector Reduces Inflammatory Damage and Behavioral Sequelae

Ist Teil von

• Molecular therapy, 2007-10, Vol.15 (10), p.1812-1819

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2007

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 β-galactosidase cDNA (HSV-β-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), β-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-β-gal and DBTC/Veh treated rats. Targeted transgene delivery and met-ENK expression successfully produced decreased inflammation in experimental pancreatitis.