Linked Life Data

19925787

Source:http://linkedlifedata.com/resource/pubmed/id/19925787

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
2010-1-27
pubmed:abstractText
Tristetraprolin (TTP) binds to AU-rich elements within the mRNAs of several inflammatory genes and causes destabilization of the target mRNAs. The protein kinase C (PKC) pathway represents a major signalling system in inflammation and PKCdelta is one of the key isoenzymes in the regulation of inflammatory processes. In the present study, we investigated the role of PKCdelta in the regulation of the expression of tristetraprolin in activated macrophages by using the PKCdelta inhibitor, rottlerin, and by downregulating PKCdelta expression by using PKCdelta siRNA. TTP protein and mRNA expression were measured by Western blotting and quantitative RT-PCR, respectively. TTP and TNFalpha mRNA decays were studied by the actinomycin D assay. In addition, we measured nuclear translocation of transcription factors believed to be important for TTP transcription, i.e. NF-kappaB, AP-2, SP1 and EGR1. Downregulation of PKCdelta by siRNA decreased significantly TTP expression in activated macrophages. Rottlerin also decreased TTP expression in wild type cells but not in cells in which PKCdelta had been downregulated by siRNA. Rottlerin decreased TTP mRNA half-life as measured by actinomycin D assay but it did not affect the nuclear translocation of transcription factors NF-kappaB, Sp1, AP-2 or EGR1 (which have been shown to be involved in TTP transcription). In addition, rottlerin reduced the decay of TNFalpha mRNA, which is an important target of TTP. The results suggest that PKCdelta up-regulates the expression of TTP by stabilizing its mRNA which may serve as a feed-back loop to regulate the inflammatory response.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1879-0712
pubmed:author
pubmed:issnType
Electronic
pubmed:day
25
pubmed:volume
628
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
220-5
pubmed:meshHeading
pubmed-meshheading:19925787-Acetophenones, pubmed-meshheading:19925787-Animals, pubmed-meshheading:19925787-Benzopyrans, pubmed-meshheading:19925787-Cell Line, pubmed-meshheading:19925787-Down-Regulation, pubmed-meshheading:19925787-Enzyme Activation, pubmed-meshheading:19925787-Gene Expression Regulation, pubmed-meshheading:19925787-Half-Life, pubmed-meshheading:19925787-Macrophages, pubmed-meshheading:19925787-Protein Kinase C-delta, pubmed-meshheading:19925787-Protein Kinase Inhibitors, pubmed-meshheading:19925787-RNA, Messenger, pubmed-meshheading:19925787-RNA, Small Interfering, pubmed-meshheading:19925787-Tetradecanoylphorbol Acetate, pubmed-meshheading:19925787-Transcription Factors, pubmed-meshheading:19925787-Tristetraprolin, pubmed-meshheading:19925787-Tumor Necrosis Factor-alpha
pubmed:year
2010
pubmed:articleTitle
Inhibition of protein kinase Cdelta reduces tristetraprolin expression by destabilizing its mRNA in activated macrophages.
pubmed:affiliation
The Immunopharmacology Research Group, University of Tampere Medical School and Research Unit, Tampere University Hospital, Tampere, Finland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't