Linked Life Data

20386470

Source:http://linkedlifedata.com/resource/pubmed/id/20386470

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2010-4-28
pubmed:abstractText
Recent studies support the idea that certain chemotherapeutic agents do not act only by cytotoxicity, but also have immunomodulatory activity. Because of their role in mitosis chemotherapeutic agents targeting microtubules are widely used, and this study determined the outcome of disturbing tubulin cytoskeleton dynamics on human dendritic cell function. Dendritic cells (DCs) play a major role in the generation of the adaptive immune response owing to their capacity for antigen presentation leading to T lymphocyte activation and differentiation and there is compelling evidence for their contribution to the antitumoral immune response. Two agents that target the tubulin cytoskeleton were used, taxol and colchicine, and a brief pretreatment with either increased antigen presentation by DCs independently of significant phenotypic change, cell death, or cytokine production. Although taxol and colchicine use different mechanisms to disrupt microtubules, NF-kappabeta was activated by either. We therefore determined whether the cytokine secretion profile in response to lipopolysaccharide (LPS) was modified. LPS stimulation of DCs induced IL-10, IL-12p70, TNFalpha and IL-1beta secretion, and taxol pretreatment modified this response by down-regulating IL-1beta secretion whereas colchicine induced a proinflammatory cytokine profile with reduced IL-10 and increased IL-12p70 and TNFalpha secretion. Taken together, these data reveal new immunomodulatory strategies of microtubule disrupting agents in dendritic cells, that of modifying the cytokine response to LPS and that of increasing T lymphocyte activation without induction of inflammatory cytokine secretion by dendritic cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1537-4513
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
364-70
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Chemotherapeutic agents targeting the tubulin cytoskeleton modify LPS-induced cytokine secretion by dendritic cells and increase antigen presentation.
pubmed:affiliation
Institut Universitaire d'Hématologie, Université Paris-Diderot-Paris 7, INSERM Unité 940, Hématologie, Immunologie, Cibles thérapeutiques, Paris, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't