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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 7
pubmed:dateCreated
2007-6-7
pubmed:abstractText
Rotavirus non-structural protein (NSP) 4 can induce aqueous secretion in the gastrointestinal tract of neonatal mice through activation of an age- and Ca(2+)-dependent plasma membrane anion permeability. Accumulating evidence suggests that nitric oxide (NO) plays a role in the modulation of aqueous secretion and the barrier function of intestinal cells. This study investigated transcriptional changes in inducible NO synthase (iNOS), an enzyme responsible for NO production, after rotavirus infection in mice and after treatment of intestinal cells with NSP4. Diarrhoea was observed in 5-day-old CD-1 mice from days 1 to 3 after inoculation with 10(7) focus-forming units of different rotavirus strains. Ileal iNOS mRNA expression was induced as early as 6 h post-inoculation, before the onset of clinical diarrhoea in infected mice, and was upregulated during the course of rotavirus-induced diarrhoea. Ex vivo treatment of ilea excised from CD-1 suckling mice with NSP4 resulted in upregulation of ileal iNOS mRNA expression within 4 h. Furthermore, NSP4 was able to induce iNOS expression and NO production in murine peritoneal macrophages and RAW264.7 cells. The specificity of NSP4 inducibility was confirmed by the inhibitory effect of anti-NSP4 serum. Using a series of truncated NSP4s, the domain responsible for iNOS induction in macrophages was mapped to the reported enterotoxin domain, aa 109-135. Thus, rotavirus infection induces ileal iNOS expression in vivo and rotavirus NSP4 also induces iNOS expression in the ileum and macrophages. Together, these findings suggest that NO plays a role in rotavirus-induced diarrhoea.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-1317
pubmed:author
pubmed:issnType
Print
pubmed:volume
88
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2064-72
pubmed:meshHeading
pubmed-meshheading:17554041-Animals, pubmed-meshheading:17554041-Animals, Newborn, pubmed-meshheading:17554041-Base Sequence, pubmed-meshheading:17554041-Cell Line, pubmed-meshheading:17554041-DNA, Complementary, pubmed-meshheading:17554041-Enterotoxins, pubmed-meshheading:17554041-Enzyme Induction, pubmed-meshheading:17554041-Glycoproteins, pubmed-meshheading:17554041-Ileum, pubmed-meshheading:17554041-Macrophages, pubmed-meshheading:17554041-Mice, pubmed-meshheading:17554041-Nitric Oxide, pubmed-meshheading:17554041-Nitric Oxide Synthase Type II, pubmed-meshheading:17554041-Protein Structure, Tertiary, pubmed-meshheading:17554041-RNA, Messenger, pubmed-meshheading:17554041-Recombinant Fusion Proteins, pubmed-meshheading:17554041-Rotavirus, pubmed-meshheading:17554041-Rotavirus Infections, pubmed-meshheading:17554041-Toxins, Biological, pubmed-meshheading:17554041-Up-Regulation, pubmed-meshheading:17554041-Viral Nonstructural Proteins, pubmed-meshheading:17554041-Virulence, pubmed-meshheading:17554041-Virus Replication
pubmed:year
2007
pubmed:articleTitle
Induction of nitric oxide synthase by rotavirus enterotoxin NSP4: implication for rotavirus pathogenicity.
pubmed:affiliation
Laboratory of Zoonotic Diseases, Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't