Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-9-18
pubmed:abstractText
In response to inflammatory stimuli, monocytes/macrophages secrete greater quantities of the proinflammatory cytokines tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and IL-6. The inflammatory process and the innate immune response are related to the activation of several transcription factors, such as nuclear factor kappaB (NF-kappaB) and activator protein 1 (AP-1). The proteasome is a multimeric protease complex, which plays a vital role in several cellular functions, including the regulation of transcription factors like NF-kappaB. In this study, we used the human monocyte cell line U937 stimulated with lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate (PMA) as a model to investigate the in vitro effects of MG132, a proteasome inhibitor, on the release of TNF-alpha, IL-1beta and IL-6 and on the expression of their membrane and soluble receptors TNF-R1, IL-1R1 and IL-6R. We also analysed the effects of MG132 on the activation of NF-kappaB and AP-1 and on the IkappaB molecule. MG132 significantly inhibited the secretion of those proinflammatory cytokines. MG132 increased the release of the soluble receptors TNF-R1 and IL-1R1 from U937 cells and decreased their cell-surface expression. MG132 also increased IL-6R cell-surface expression and decreased its release. Proteasome inhibition also led to an increase in LPS+PMA-induced AP-1 activation and the attenuation of LPS+PMA-induced IkappaB degradation, resulting in the abolition of NF-kappaB activation. Our experiments strongly suggest that the proteasome is an important factor in the regulation of proinflammatory cytokines and their receptors.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/18298552-10223331, http://linkedlifedata.com/resource/pubmed/commentcorrection/18298552-10922424, http://linkedlifedata.com/resource/pubmed/commentcorrection/18298552-11032838, http://linkedlifedata.com/resource/pubmed/commentcorrection/18298552-11086075, http://linkedlifedata.com/resource/pubmed/commentcorrection/18298552-11780554, http://linkedlifedata.com/resource/pubmed/commentcorrection/18298552-11927288, http://linkedlifedata.com/resource/pubmed/commentcorrection/18298552-12700891, http://linkedlifedata.com/resource/pubmed/commentcorrection/18298552-12706294, http://linkedlifedata.com/resource/pubmed/commentcorrection/18298552-12874245, http://linkedlifedata.com/resource/pubmed/commentcorrection/18298552-15135296, http://linkedlifedata.com/resource/pubmed/commentcorrection/18298552-15494479, http://linkedlifedata.com/resource/pubmed/commentcorrection/18298552-15564374, http://linkedlifedata.com/resource/pubmed/commentcorrection/18298552-15731011, http://linkedlifedata.com/resource/pubmed/commentcorrection/18298552-15769896, http://linkedlifedata.com/resource/pubmed/commentcorrection/18298552-15786731, http://linkedlifedata.com/resource/pubmed/commentcorrection/18298552-15888915, http://linkedlifedata.com/resource/pubmed/commentcorrection/18298552-16175180, http://linkedlifedata.com/resource/pubmed/commentcorrection/18298552-16267367, http://linkedlifedata.com/resource/pubmed/commentcorrection/18298552-16531564, http://linkedlifedata.com/resource/pubmed/commentcorrection/18298552-16565325, http://linkedlifedata.com/resource/pubmed/commentcorrection/18298552-16670341, http://linkedlifedata.com/resource/pubmed/commentcorrection/18298552-16737962, http://linkedlifedata.com/resource/pubmed/commentcorrection/18298552-16864405, http://linkedlifedata.com/resource/pubmed/commentcorrection/18298552-16965564, http://linkedlifedata.com/resource/pubmed/commentcorrection/18298552-178611, http://linkedlifedata.com/resource/pubmed/commentcorrection/18298552-2537297, http://linkedlifedata.com/resource/pubmed/commentcorrection/18298552-2824494, http://linkedlifedata.com/resource/pubmed/commentcorrection/18298552-6828386, http://linkedlifedata.com/resource/pubmed/commentcorrection/18298552-7622446, http://linkedlifedata.com/resource/pubmed/commentcorrection/18298552-7951753, http://linkedlifedata.com/resource/pubmed/commentcorrection/18298552-8327496, http://linkedlifedata.com/resource/pubmed/commentcorrection/18298552-9789328
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Proteinase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Cytokines, http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Proteins, http://linkedlifedata.com/resource/pubmed/chemical/IL1R1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/IL6R protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Inflammation Mediators, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1beta, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6, http://linkedlifedata.com/resource/pubmed/chemical/Leupeptins, http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides, http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytokine, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-1 Type I, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-6, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor..., http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha, http://linkedlifedata.com/resource/pubmed/chemical/benzyloxycarbonylleucyl-leucyl-leuci...
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1365-2567
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
124
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
534-41
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
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