Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-7-22
pubmed:abstractText
We have previously presented evidence demonstrating that mice deficient in NF-kappaB subunits are susceptible to colitis induced by the pathogenic enterohepatic Helicobacter species, H. hepaticus. However, it has not been determined whether NF-kappaB is required within inhibitory lymphocyte populations, within cells of the innate immune system, or both, to suppress inflammation. To examine these issues, we have performed a series of adoptive transfer experiments using recombination-activating gene (Rag)-2(-/-) or p50(-/-)p65(+/-)Rag-2(-/-) mice as hosts for wild-type (WT) and p50(-/-)p65(+/-) lymphocyte populations. We have shown that although the ability of H. hepaticus to induce colitis in Rag-2(-/-) mice is inhibited by the presence of either WT or p50(-/-)p65(+/-) splenocytes, these splenocyte populations are unable to suppress H. hepaticus-induced colitis in p50(-/-)p65(+/-)Rag-2(-/-) mice. Colitis in these animals is characterized by increased expression of inflammatory cytokines including IL-12 p40, and depletion of IL-12 p40 from p50(-/-)p65(+/-) mice ameliorates H. hepaticus-induced disease. Consistent with a primary defect in the regulation of IL-12 expression, H. hepaticus induced markedly higher levels of IL-12 p40 in p50(-/-)p65(+/-) macrophages than in WT macrophages. These results suggest that inhibition of H. hepaticus-induced IL-12 p40 expression by NF-kappaB subunits is critical to preventing colonic inflammation in response to inflammatory microflora.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
171
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1484-92
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12874241-Adoptive Transfer, pubmed-meshheading:12874241-Animals, pubmed-meshheading:12874241-Bone Marrow Cells, pubmed-meshheading:12874241-Colitis, pubmed-meshheading:12874241-DNA-Binding Proteins, pubmed-meshheading:12874241-Helicobacter, pubmed-meshheading:12874241-Immune Sera, pubmed-meshheading:12874241-Immunity, Innate, pubmed-meshheading:12874241-Injections, Intraperitoneal, pubmed-meshheading:12874241-Interleukin-12, pubmed-meshheading:12874241-Interleukin-12 Subunit p40, pubmed-meshheading:12874241-Intestinal Mucosa, pubmed-meshheading:12874241-Lymphocyte Subsets, pubmed-meshheading:12874241-Macrophages, pubmed-meshheading:12874241-Mice, pubmed-meshheading:12874241-Mice, Inbred C57BL, pubmed-meshheading:12874241-Mice, Knockout, pubmed-meshheading:12874241-NF-kappa B, pubmed-meshheading:12874241-Protein Subunits, pubmed-meshheading:12874241-Spleen, pubmed-meshheading:12874241-Up-Regulation
pubmed:year
2003
pubmed:articleTitle
NF-kappa B is required within the innate immune system to inhibit microflora-induced colitis and expression of IL-12 p40.
pubmed:affiliation
Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't