PMID- 20461064
OWN - NLM
STAT- MEDLINE
DCOM- 20100930
LR  - 20240324
IS  - 1525-0024 (Electronic)
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 18
IP  - 7
DP  - 2010 Jul
TI  - Vasoactive intestinal peptide increases hepatic transduction and reduces innate 
      immune response following administration of helper-dependent Ad.
PG  - 1339-45
LID - 10.1038/mt.2010.84 [doi]
AB  - Helper-dependent adenoviral vectors (HDAd) are effective tools for liver-directed 
      gene therapy because they can mediate long-term transgene expression in the 
      absence of chronic toxicity. However, high vector doses required for efficient 
      hepatocyte transduction by intravascular delivery result in systemic vector 
      dissemination and dose-dependent activation of the innate immunity. Therefore, 
      strategies to achieve high-efficiency hepatocyte transduction using low vector 
      doses and/or to reduce the acute elevations of proinflammatory cytokines and 
      chemokines may have significant clinical potential. Vasoactive intestinal peptide 
      (VIP) is an endogenous neuropeptide involved in the regulation of hepatic blood 
      flow and plays an important role as modulator of immune functions. Here, we show 
      that VIP pretreatment in mice is able to increase hepatocyte transduction by 
      HDAd, decrease vector uptake by the spleen, reduce elevation of proinflammatory 
      serum cytokines interleukin (IL)-6 and IL-12, and reduce serum levels of 
      aspartate aminotransferase (AST) and alanine aminotransferase (ALT) following 
      intravenous HDAd injection. VIP pretreatment also resulted in a reduction in the 
      expression of the chemokines macrophage-inflammatory protein 2 (MIP-2), monocyte 
      chemotactic protein 1 (MCP-1), and regulated on activation normal T-cell 
      expressed and secreted (RANTES) in the livers of mice injected with HDAd. These 
      results suggest that VIP can improve the therapeutic index of HDAd by increasing 
      hepatocyte transduction efficiency while reducing cytokine and chemokine 
      expression following intravascular delivery of HDAd.
FAU - Vetrini, Francesco
AU  - Vetrini F
AD  - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, 
      Texas 77030, USA.
FAU - Brunetti-Pierri, Nicola
AU  - Brunetti-Pierri N
FAU - Palmer, Donna J
AU  - Palmer DJ
FAU - Bertin, Terry
AU  - Bertin T
FAU - Grove, Nathan C
AU  - Grove NC
FAU - Finegold, Milton J
AU  - Finegold MJ
FAU - Ng, Philip
AU  - Ng P
LA  - eng
GR  - R01 DK067324/DK/NIDDK NIH HHS/United States
GR  - R00 DK077447/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100511
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 0 (Cytokines)
RN  - 187348-17-0 (Interleukin-12)
RN  - 37221-79-7 (Vasoactive Intestinal Peptide)
SB  - IM
MH  - Adenoviridae/*genetics
MH  - Animals
MH  - Cytokines/metabolism
MH  - Genetic Vectors/*administration & dosage/genetics
MH  - Interleukin-12/metabolism
MH  - Liver/*drug effects/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Polymerase Chain Reaction
MH  - Spleen/drug effects/metabolism
MH  - Transduction, Genetic
MH  - Vasoactive Intestinal Peptide/*pharmacology
PMC - PMC2911263
EDAT- 2010/05/13 06:00
MHDA- 2010/10/01 06:00
PMCR- 2011/07/01
CRDT- 2010/05/13 06:00
PHST- 2010/05/13 06:00 [entrez]
PHST- 2010/05/13 06:00 [pubmed]
PHST- 2010/10/01 06:00 [medline]
PHST- 2011/07/01 00:00 [pmc-release]
AID - S1525-0016(16)31079-6 [pii]
AID - 10.1038/mt.2010.84 [doi]
PST - ppublish
SO  - Mol Ther. 2010 Jul;18(7):1339-45. doi: 10.1038/mt.2010.84. Epub 2010 May 11.