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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1997-7-22
pubmed:abstractText
In recent studies we have shown that the expression of stem cell factor (SCF) in human endothelial cells is regulated by inflammatory processes. Gram-negative bacteria, interleukin-1 (IL-1), and lipopolysaccharide were able to upregulate the expression of SCF in human umbilical vein endothelial cells (HUVEC) (Blood 83:2836, 1994). Interestingly enough c-kit, the receptor of SCF, is coexpressed on HUVEC, suggesting an autoregulatory mechanism. To investigate the relation of c-kit and inflammatory processes we stimulated HUVEC with IL-1alpha and we established an in vitro model of inflammation. Binding experiments with 125I-SCF were performed to study the c-kit receptor expression on HUVEC. Scatchard analysis revealed both high-affinity receptors (K(d) approximately 0.36 nmol/L) and low-affinity receptors (K(d) approximately 2.9 nmol/L). Exposure to IL-1alpha led to a significant 50% reduction of c-kit high-affinity receptors, whereas the number of low-affinity receptors was not affected, in comparison to a control group of untreated HUVEC. Furthermore, using Northern blot analysis we studied the regulation c-kit mRNA expression in HUVEC after stimulation with IL-1alpha. Kinetic experiments showed a time-dependent downregulation of c-kit specific transcripts. In addition, we cocultured HUVEC with diverse bacterial strains. Experiments were performed over time with 1 x 10(6) bacteria/mL. Our data showed that, in contrary to the previously reported upregulation of SCF mRNA expression, stimulation with Yersinia enterocolitica or with Neisseria meningitidis led to a significant time-dependent downregulation of c-kit mRNA within 3 hours. These data indicate that inflammatory stimuli such as IL-1 or living bacteria activate a mechanism that downregulates c-kit receptor expression in human endothelial cells during the state of inflammation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
90
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
148-55
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Downregulation of c-kit expression in human endothelial cells by inflammatory stimuli.
pubmed:affiliation
Department of Pediatric Hematology and Oncology, Children's Hospital, Medical School Hannover, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't