Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2002-2-22
pubmed:abstractText
Although well recognized for its anti-inflammatory effect on gene expression in stimulated monocytes and macrophages, IL-4 is a pleiotropic cytokine that has also been shown to enhance TNF-alpha and IL-12 production in response to stimulation with LPS. In the present study we expand these prior studies in three areas. First, the potentiating effect of IL-4 pretreatment is both stimulus and gene selective. Pretreatment of mouse macrophages with IL-4 for a minimum of 6 h produces a 2- to 4-fold enhancement of LPS-induced expression of several cytokines and chemokines, including TNF-alpha, IL-1alpha, macrophage-inflammatory protein-2, and KC, but inhibits the production of IL-12p40. In addition, the production of TNF-alpha by macrophages stimulated with IFN-gamma and IL-2 is inhibited by IL-4 pretreatment, while responses to both LPS and dsRNA are enhanced. Second, the ability of IL-4 to potentiate LPS-stimulated cytokine production appears to require new IL-4-stimulated gene expression, because it is time dependent, requires the activation of STAT6, and is blocked by the reversible protein synthesis inhibitor cycloheximide during the IL-4 pretreatment period. Finally, IL-4-mediated potentiation of TNF-alpha production involves specific enhancement of mRNA translation. Although TNF-alpha protein is increased in IL-4-pretreated cells, the level of mRNA remains unchanged. Furthermore, LPS-stimulated TNF-alpha mRNA is selectively enriched in actively translating large polyribosomes in IL-4-pretreated cells compared with cells stimulated with LPS alone.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
168
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2456-63
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11859138-Animals, pubmed-meshheading:11859138-Cells, Cultured, pubmed-meshheading:11859138-Chemokines, pubmed-meshheading:11859138-Cytokines, pubmed-meshheading:11859138-Drug Synergism, pubmed-meshheading:11859138-Interleukin-4, pubmed-meshheading:11859138-Kinetics, pubmed-meshheading:11859138-Lipopolysaccharides, pubmed-meshheading:11859138-Macrophages, Peritoneal, pubmed-meshheading:11859138-Mice, pubmed-meshheading:11859138-Mice, Inbred C57BL, pubmed-meshheading:11859138-Mice, Knockout, pubmed-meshheading:11859138-Protein Biosynthesis, pubmed-meshheading:11859138-RNA, Messenger, pubmed-meshheading:11859138-STAT6 Transcription Factor, pubmed-meshheading:11859138-Trans-Activators, pubmed-meshheading:11859138-Transcriptional Activation, pubmed-meshheading:11859138-Tumor Necrosis Factor-alpha
pubmed:year
2002
pubmed:articleTitle
IL-4 pretreatment selectively enhances cytokine and chemokine production in lipopolysaccharide-stimulated mouse peritoneal macrophages.
pubmed:affiliation
Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.