Linked Life Data

16394015

Source:http://linkedlifedata.com/resource/pubmed/id/16394015

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-1-5
pubmed:abstractText
Helicobacter hepaticus is an enterohepatic Helicobacter species that induces lower bowel inflammation in susceptible mouse strains, including those lacking the p50/p105 subunit of NF-kappaB. H. hepaticus-induced colitis is associated with elevated levels of IL-12 p40 expression, and p50/p105-deficient macrophages express higher levels of IL-12 p40 than wild-type macrophages after challenge with H. hepaticus. However, the molecular mechanisms by which the p50/p105 subunit of NF-kappaB suppresses IL-12 p40 expression have not yet been elucidated. In this study we have demonstrated that H. hepaticus challenge of macrophages induces ERK activation, and this event plays a critical role in inhibiting the ability of H. hepaticus to induce IL-12 p40. Activation of ERK requires both p50/p105 and the MAPK kinase kinase, Tpl-2. Inhibition of the induction of IL-12 p40 by ERK was independent of c-Rel, a known positive regulator of IL-12 p40. Instead, it was linked to the induction of c-Fos, a known inhibitor of IL-12 p40 expression. These results suggest that H. hepaticus induces ERK activation by a pathway dependent upon Tpl-2 and p105, and that activation of ERK inhibits the expression of IL-12 p40 by inducing c-Fos. Thus, a defect in ERK activation could play a pivotal role in the superinduction of IL-12 p40 observed after challenge of macrophages lacking the p50/p105 subunit of NF-kappaB with H. hepaticus.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
176
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1244-51
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16394015-Animals, pubmed-meshheading:16394015-Butadienes, pubmed-meshheading:16394015-Enzyme Activation, pubmed-meshheading:16394015-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:16394015-Helicobacter hepaticus, pubmed-meshheading:16394015-Interleukin-10, pubmed-meshheading:16394015-Interleukin-12, pubmed-meshheading:16394015-Interleukin-12 Subunit p40, pubmed-meshheading:16394015-MAP Kinase Signaling System, pubmed-meshheading:16394015-Macrophages, pubmed-meshheading:16394015-Mice, pubmed-meshheading:16394015-Mice, Inbred C57BL, pubmed-meshheading:16394015-Mice, Knockout, pubmed-meshheading:16394015-NF-kappa B p50 Subunit, pubmed-meshheading:16394015-Nitriles, pubmed-meshheading:16394015-Protein Kinase Inhibitors, pubmed-meshheading:16394015-Protein Subunits, pubmed-meshheading:16394015-Proto-Oncogene Proteins c-fos
pubmed:year
2006
pubmed:articleTitle
Defective activation of ERK in macrophages lacking the p50/p105 subunit of NF-kappaB is responsible for elevated expression of IL-12 p40 observed after challenge with Helicobacter hepaticus.
pubmed:affiliation
Immunology Research Division, Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural