rdf:type |
|
lifeskim:mentions |
umls-concept:C0007634,
umls-concept:C0017262,
umls-concept:C0026473,
umls-concept:C0031715,
umls-concept:C0040648,
umls-concept:C0085295,
umls-concept:C0086418,
umls-concept:C0178719,
umls-concept:C0185117,
umls-concept:C0205263,
umls-concept:C0220781,
umls-concept:C0752312,
umls-concept:C0851285,
umls-concept:C1366765,
umls-concept:C1370600,
umls-concept:C1883254,
umls-concept:C2911684
|
pubmed:issue |
42
|
pubmed:dateCreated |
2006-10-16
|
pubmed:abstractText |
Human immunodeficiency virus (HIV)-Tat plays an important role in virus replication and in various aspects of host immune responses, including dysregulation of cytokine production. IL-10, an anti-inflammatory cytokine, is up-regulated during the course of HIV infection representing an important pathway by which HIV may induce immunodeficiency. Here we show that extracellular as well as intracellular Tat induced IL-10 expression in normal human monocytes and promonocytic THP-1 cells. The signaling pathways involved in the regulation of IL-10 production by endogenous Tat remain unknown. To understand the molecular mechanism underlying intracellular Tat-induced IL-10 transcription, we employed a retroviral expression system to investigate the role of MAPKs and the transcription factor(s) involved. Our results suggest that an inhibitor specific for the ERK1/2, PD98059, selectively blocked intracellular Tat-induced IL-10 expression in THP-1 cells. Furthermore, intracellular Tat activated the CREB-1 transcription factor through Ser(133) phosphorylation that was regulated by ERK MAPK as determined by IL-10 promoter analysis and gel shift assays. Overall, our results suggest that intracellular HIV-Tat induces IL-10 transcription by ERK MAPK-dependent CREB-1 transcription factor activation through Ser(133) phosphorylation.
|
pubmed:language |
eng
|
pubmed:journal |
|
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CREB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP Response...,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Gene Products, tat,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-10,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Serine
|
pubmed:status |
MEDLINE
|
pubmed:month |
Oct
|
pubmed:issn |
0021-9258
|
pubmed:author |
|
pubmed:issnType |
Print
|
pubmed:day |
20
|
pubmed:volume |
281
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
31647-58
|
pubmed:dateRevised |
2009-11-19
|
pubmed:meshHeading |
pubmed-meshheading:16920714-Cyclic AMP Response Element-Binding Protein,
pubmed-meshheading:16920714-DNA Primers,
pubmed-meshheading:16920714-Enzyme Inhibitors,
pubmed-meshheading:16920714-Gene Products, tat,
pubmed-meshheading:16920714-Humans,
pubmed-meshheading:16920714-Interleukin-10,
pubmed-meshheading:16920714-Luciferases,
pubmed-meshheading:16920714-MAP Kinase Signaling System,
pubmed-meshheading:16920714-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:16920714-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:16920714-Monocytes,
pubmed-meshheading:16920714-Phosphorylation,
pubmed-meshheading:16920714-Retroviridae,
pubmed-meshheading:16920714-Serine
|
pubmed:year |
2006
|
pubmed:articleTitle |
Intracellular HIV-Tat expression induces IL-10 synthesis by the CREB-1 transcription factor through Ser133 phosphorylation and its regulation by the ERK1/2 MAPK in human monocytic cells.
|
pubmed:affiliation |
Department of Pathology, Division of Virology, Research Institute, Children's Hospital of Eastern Ontario, Ottawa K1H 8L1, Canada.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|