Linked Life Data

12946945

Source:http://linkedlifedata.com/resource/pubmed/id/12946945

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2003-9-22
pubmed:abstractText
We previously reported that treatment of human vascular smooth muscle cells (SMCs) with proapoptotic stimuli, including Fas ligand plus cycloheximide (FasL/Chx), or overexpression of Fas-associated death domain protein (FADD) result in increased expression of monocyte chemoattractant protein-1 (MCP-1) and other proinflammatory genes. In this study, we demonstrate that Fas/FADD-induced MCP-1 upregulation is driven by an autocrine/paracrine signaling loop in which interleukin (IL)-1alpha synthesis and release are activated through caspase- and calpain-dependent processes. Untreated SMCs contain very little IL-1alpha protein or transcript. Both were increased greatly in response to Fas/FADD activation, primarily through an autocrine/paracrine pathway in which secreted IL-1alpha stimulated additional IL-1alpha synthesis and release. Caspase 8 (Csp8) activity increased in response to FasL/Chx treatment, and Csp8 inhibitors markedly reduced IL-1alpha release and MCP-1 upregulation. In contrast, Csp8 activity was not significantly increased in response to FADD overexpression and caspase inhibitors did not effect FADD-induced MCP-1 upregulation. Both FasL/Chx treatment and FADD overexpression increased the activity of calpains. Calpain inhibitors reduced IL-1alpha release and MCP-1 upregulation in both FADD-overexpressing SMCs and FasL/Chx-treated SMCs without blocking Csp8 activity. This indicates that calpains are not required for activation of caspases and that caspase activation is not sufficient for IL-1alpha release and MCP-1 upregulation. These data suggest that calpains play a dominant role in Fas/FADD-induced IL-1alpha release and MCP-1 upregulation and that caspase activation may function to amplify the effects of calpain activation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing, http://linkedlifedata.com/resource/pubmed/chemical/Calpain, http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Caspases, http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL2, http://linkedlifedata.com/resource/pubmed/chemical/Cycloheximide, http://linkedlifedata.com/resource/pubmed/chemical/FADD protein, human, http://linkedlifedata.com/resource/pubmed/chemical/FASLG protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Fas Ligand Protein, http://linkedlifedata.com/resource/pubmed/chemical/Fas-Associated Death Domain Protein, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
19
pubmed:volume
93
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
515-22
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12946945-Adaptor Proteins, Signal Transducing, pubmed-meshheading:12946945-Calpain, pubmed-meshheading:12946945-Carrier Proteins, pubmed-meshheading:12946945-Caspases, pubmed-meshheading:12946945-Cells, Cultured, pubmed-meshheading:12946945-Chemokine CCL2, pubmed-meshheading:12946945-Cycloheximide, pubmed-meshheading:12946945-Fas Ligand Protein, pubmed-meshheading:12946945-Fas-Associated Death Domain Protein, pubmed-meshheading:12946945-Gene Expression Regulation, pubmed-meshheading:12946945-Humans, pubmed-meshheading:12946945-Interleukin-1, pubmed-meshheading:12946945-Membrane Glycoproteins, pubmed-meshheading:12946945-Muscle, Smooth, Vascular, pubmed-meshheading:12946945-Signal Transduction, pubmed-meshheading:12946945-Transcription, Genetic, pubmed-meshheading:12946945-Up-Regulation
pubmed:year
2003
pubmed:articleTitle
Fas and Fas-associated death domain protein regulate monocyte chemoattractant protein-1 expression by human smooth muscle cells through caspase- and calpain-dependent release of interleukin-1alpha.
pubmed:affiliation
Department of Pathology, University of Washington, Box 357470, Seattle, Wash 98195-7470, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.