Linked Life Data

21229240

Source:http://linkedlifedata.com/resource/pubmed/id/21229240

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-3-31
pubmed:abstractText
Macrophages (m?) from pre-diseased mice of the major murine inbred models of spontaneous autoimmunity (AI), including multiple lupus-prone strains and the type I diabetes-prone NOD (non-obese diabetic) strain, have identical apoptotic target-dependent abnormalities. This characteristic feature of m? from AI-prone mice suggests that abnormal signaling events induced within m? following their interaction with apoptotic targets may predispose to AI. Such signaling abnormalities would affect predominantly the processing and presentation of self-antigen (i.e., derived from apoptotic targets), while sparing the processing and presentation of foreign antigen (i.e., derived from non-apoptotic sources). Here, we used DNA microarrays to test the hypothesis that m? from AI-prone mice (MRL/MpJ [MRL/+] or MRL/MpJ-Tnfrsf6 ( lpr ) [MRL/lpr]) differentially express multiple genes in comparison to non-AI m? (BALB/c), but do so in a largely apoptotic cell-dependent manner. M? were stimulated with lipopolysaccharide, a potent innate stimulus, in the presence or absence of serum (an experimental surrogate for apoptotic targets). In accord with our hypothesis, the number of genes differentially expressed by MRL m? was significantly increased in the presence vs. the absence of serum, the apoptotic target surrogate (n?=?401 vs. n?=?201). Notably, for genes differentially expressed by MRL m? in the presence of serum, serum-free culture normalized their expression to a level statistically indistinguishable from that by non-AI m?. Comparisons of m? from AI-prone NOD and non-AI C57BL/6 mice corroborated these findings. Together, these data support the hypothesis that m? from MRL and other AI-prone mice are characterized by a conditional abnormality elicited by serum lipids or apoptotic targets.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1432-1211
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
63
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
291-308
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Macrophages from lupus-prone MRL mice have a conditional signaling abnormality that leads to dysregulated expression of numerous genes.
pubmed:affiliation
Department of Biology, Kutztown University of Pennsylvania, Kutztown, PA 19530, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural