Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1999-1-21
pubmed:abstractText
Vitamin D and retinoids cooperate to inhibit the proliferation and induce the differentiation of human myelomonocytic U937 leukemia cells. In the present work, we investigated the role of TGF-beta as an endogenous mediator of this process. We found that the TGF-beta1 precursor began to accumulate in cell culture supernatants soon after the addition of 1alpha,25 dihydroxyvitamin D3 (VD) and retinoids. We used neutralizing antibodies (AbTGF-beta) and antisense oligonucleotide (AS Oligo) to inhibit its possible effects. Our data demonstrated that AbTGF-beta partially inhibit the expression of the differentiated phenotype, as assessed by measurement of phagocytic activity, response to the chemotactic peptide fMLP, and lysozyme secretion. AS Oligo was also inhibitory, and the effects of AS Oligo and AbTGF-beta were cumulative. Cell growth inhibition induced by VD and retinoids was completely reversed, and differentiation was reduced by about 75% when both inhibitors were associated. Time course experiments based on the delayed addition of AbTGF-beta and AS Oligo showed that TGF-beta1 was required for cell differentiation 24 h after the addition of inducers. Studies on TGF-beta receptors revealed that, while the expression of type II receptor was stable, the level of type I TGF-beta receptor mRNA and the expression of the protein began to decline early during the differentiation process. As a whole, these results support the notion that an autocrine TGF-beta pathway, activated by VD and retinoids in U937 cells, is involved in the early steps of the process leading to cell growth arrest and differentiation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0021-9541
pubmed:author
pubmed:issnType
Print
pubmed:volume
178
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
109-19
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Transforming growth factor-beta1 is an autocrine mediator of U937 cell growth arrest and differentiation induced by vitamin D3 and retinoids.
pubmed:affiliation
EMBL, Department of Cell Biology, Heidelberg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't