Linked Life Data

15383564

Source:http://linkedlifedata.com/resource/pubmed/id/15383564

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2004-9-22
pubmed:abstractText
PGE(2), synthesized by cyclooxygenase-2 (COX-2)-overexpressing tumor, is known to contribute to cellular immune suppression in cancer patients, but the mechanism remains unclear. We report the mechanism of a CD4(+) T regulatory type 1 (Tr1) induction by CD11c(+) mature dendritic cells (DCs) that phagocytose allogeneic and autologous COX-2-overexpressing glioma. A human glioma cell line, U-87MG, and primary cultured glioblastoma cells (MG-377) overexpressed COX-2. We did not detect IL-10Ralpha expression in these gliomas, and rIL-10 did not suppress their COX-2 expression. Exposure to COX-2-overexpressing glioma induced mature DCs to overexpress IL-10 and decreased IL-12p70 production. These DCs induced a Tr1 response, which is characterized by robust secretion of IL-10 and TGF-beta with negligible IL-4 secretion by CD4(+) T cells, and an inhibitory effect on admixed lymphocytes. Peripheral CD4(+) T cell populations isolated from an MG-377 patient also predominantly demonstrated a Tr1 response against MG-377 cells. Selective COX-2 inhibition in COX-2-overexpressing gliomas at the time of phagocytic uptake by DCs abrogated this regulatory response and instead elicited Th1 activity. COX-2 stable transfectants in LN-18 (LN-18-COX2) also induced a Tr1 response. The effect of a COX-2 inhibition in LN-18-COX2 is reversible after administration of PGE(2). Taken together, robust levels of PGE(2) from COX-2-overexpressing glioma, which is unresponsive to IL-10 within the local microenvironment, may cause DCs to secrete high levels of IL-10. These results indicate that COX-2-overexpressing tumors induce a Tr1 response, which is mediated by tumor-exposed, IL-10-enhanced DCs.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
173
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4352-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15383564-Apoptosis, pubmed-meshheading:15383564-Cell Differentiation, pubmed-meshheading:15383564-Cell Line, Tumor, pubmed-meshheading:15383564-Cells, Cultured, pubmed-meshheading:15383564-Coculture Techniques, pubmed-meshheading:15383564-Cyclooxygenase 2, pubmed-meshheading:15383564-Dendritic Cells, pubmed-meshheading:15383564-Dinoprostone, pubmed-meshheading:15383564-Glioma, pubmed-meshheading:15383564-Humans, pubmed-meshheading:15383564-Interleukin-10, pubmed-meshheading:15383564-Isoantigens, pubmed-meshheading:15383564-Isoenzymes, pubmed-meshheading:15383564-Lymphocyte Activation, pubmed-meshheading:15383564-Membrane Proteins, pubmed-meshheading:15383564-Phagocytosis, pubmed-meshheading:15383564-Prostaglandin-Endoperoxide Synthases, pubmed-meshheading:15383564-Receptors, Interleukin, pubmed-meshheading:15383564-Receptors, Interleukin-10, pubmed-meshheading:15383564-T-Lymphocytes, Regulatory, pubmed-meshheading:15383564-Up-Regulation
pubmed:year
2004
pubmed:articleTitle
Induction of a CD4+ T regulatory type 1 response by cyclooxygenase-2-overexpressing glioma.
pubmed:affiliation
Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.