Linked Life Data

16365418

Source:http://linkedlifedata.com/resource/pubmed/id/16365418

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-12-20
pubmed:abstractText
IL-12 drives type I immune responses and can mediate chronic inflammation that leads to host defense as well as disease. Recently, we discovered a novel role for 12/15-lipoxygenase (12/15-LO) in mediating IL-12p40 expression in atherosclerotic plaque and in isolated macrophages. We now demonstrate that 12/15-LO regulates IL-12 family cytokine production in a cell-type and stimulus-restricted fashion. LPS-stimulated elicited peritoneal macrophages derived from 12/15-LO-deficient (Alox15) mice produced reduced IL-12 and IL-23 levels, but comparable amounts of several other inflammatory mediators tested. Furthermore, LPS stimulation triggered an increase in wild-type macrophage 12/15-LO activity, whereas pharmacological inhibition of 12/15-LO activity suppressed LPS-induced IL-12 production in wild-type macrophages. 12/15-LO-deficient macrophages also produced reduced levels of IL-12 in response to TLR2 stimulation, but not in response to CpG (TLR9) or CD40/CD40L-mediated activation. In contrast to our previous finding of reduced IL-12 production in the setting of atherosclerosis, we found that comparable IL-12 levels were produced in Alox15 and wild-type mice during an acute response to LPS in vivo. This paradox may be explained by normal production of IL-12 by 12/15-LO-deficient neutrophils and dendritic cells, which are major sources of IL-12 during acute inflammation. Finally, we detected selectively decreased association of the transcription factors IFN consensus sequence binding protein and NF-kappaB with the IL-12p40 promoter in 12/15-LO-deficient macrophages. Taken together, these findings reveal a highly selective pathway to IL-12 production that may prove a useful target in chronic inflammation while sparing the acute response to infection.
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
1
pubmed:volume
176
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
265-74
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:16365418-Animals, pubmed-meshheading:16365418-Arachidonate 12-Lipoxygenase, pubmed-meshheading:16365418-Arachidonate 15-Lipoxygenase, pubmed-meshheading:16365418-Cells, Cultured, pubmed-meshheading:16365418-Cytokines, pubmed-meshheading:16365418-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:16365418-Female, pubmed-meshheading:16365418-Humans, pubmed-meshheading:16365418-Interferon Regulatory Factors, pubmed-meshheading:16365418-Interferon-gamma, pubmed-meshheading:16365418-Interleukin-12, pubmed-meshheading:16365418-Macrophage Activation, pubmed-meshheading:16365418-Macrophages, Peritoneal, pubmed-meshheading:16365418-Male, pubmed-meshheading:16365418-Mice, pubmed-meshheading:16365418-NF-kappa B, pubmed-meshheading:16365418-Protein Subunits, pubmed-meshheading:16365418-Reverse Transcriptase Polymerase Chain Reaction
pubmed:year
2006
pubmed:articleTitle
Cellular and molecular mechanisms of the selective regulation of IL-12 production by 12/15-lipoxygenase.
pubmed:affiliation
The Wistar Institute, Philadelphia, PA 19104, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural