Amelioration of dextran sulfate sodium-induced colitis by neuropeptide Y antisense oligodeoxynucleotide.
BACKGROUND
Neuropeptide Y (NPY) from enteric neurons has been shown to play an important role in immune and inflammatory responses. The purpose of the present study was to investigate the effects of NPY antisense oligodeoxynucleotides (ODNs) on an experimental model of ulcerative colitis (UC).


METHODS
NPY antisense ODNs were administered in experimental colitis induced by dextran sulfate sodium (DSS). The disease activity index (DAI) and histological score were observed. The tumor necrosis factor (TNF)-alpha and NPY levels were measured by enzyme-linked immunosorbent assay. Phosphorylated Akt (p-Akt) expression was determined by immunohistochemical staining. Activated nuclear factor (NF)-kappaB was assessed by western blot analysis. Myeloperoxidase (MPO) activity was determined by using MPO assay kit.


RESULTS
A significant improvement was observed in DAI and histological score in rats with NPY antisense ODNs, and the increase in NPY and TNF-alpha levels, MPO activity, and the expression p-Akt and p-NF-kappaB in rats with DSS-induced colitis was significantly reduced following the administration of NPY antisense ODNs.


CONCLUSIONS
The administration of NPY antisense ODNs leads to an amelioration of DSS-induced colitis, suggesting that NPY plays an important role in modulating inflammation in colitis, and NPY antisense ODNs may be a useful therapeutic approach to the treatment of UC.
Department of Geriatrics Medicine and Gastroenterology, West China Hospital, Sichuan University, Chengdu, 61004 Sichuan, China.
Xue Hua
XH
Pang
Tian Ke
TK
Li
Qin
Q
Xie
Fu Qian
FQ
He
De Jun
DJ
Cui
You Qin
YQ
Chen
Xiao Li
XL
Huang
Hua Tian
HT
Gan
D000818:Animals; D003092:Colitis / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D016264:Dextran Sulfate; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology / Q000627:therapeutic use*; D009195:Peroxidase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D009478:Neuropeptide Y; D009838:Oligodeoxyribonucleotides; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D016264:Dextran Sulfate; D009195:Peroxidase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D016650:Fluorescein-5-isothiocyanate