Linked Life Data

21673072

Source:http://linkedlifedata.com/resource/pubmed/id/21673072

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-8-23
pubmed:abstractText
Allogeneic hematopoietic cell transplantation (HCT) is widely used to treat patients with life-threatening malignant and nonmalignant hematological diseases. However, allogeneic HCT often is accompanied by severe and lethal complications from graft-versus-host disease (GVHD), in which activated donor T cells recognize histocompatibility antigenic mismatches and cause significant toxicity in the recipient. In the current study, we tested the hypothesis that activation of cannabinoid receptors on donor-derived T cells may prevent GVHD. We tested the effect of ?(9)-tetrahydrocannabinol (THC) in an acute model of GVHD that was induced by transferring parental C57BL/6 (B6) spleen cells into (C57BL/6 × DBA/2) F(1)(BDF1) mice. Transfer of B6 cells into BDF1 mice produced severe acute GVHD in the recipient, characterized by lymphoid hyperplasia, weight loss, T helper l cytokine production and mortality. THC administration led to early recovery from body weight loss, reduced tissue injury in the liver and intestine, as well as complete survival. THC treatment reduced the expansion of donor-derived effector T cells and blocked the killing of host-derived immune cells while promoting Foxp3(+) regulatory T cells. Impaired hematopoiesis seen during GVHD was rescued by treatment with THC. The ability of THC to reduce the clinical GVHD was reversed, at least in part, by administration of cannabinoid receptor (CB) 1 and CB2 antagonists, thereby demonstrating that THC-mediated amelioration of GVHD was cannabinoid receptor-dependent. Our results demonstrate for the first time that targeting cannabinoid receptors may constitute a novel treatment modality against acute GVHD.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1521-0103
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
338
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
819-28
pubmed:meshHeading
pubmed-meshheading:21673072-Animals, pubmed-meshheading:21673072-Antibodies, Monoclonal, pubmed-meshheading:21673072-Bone Marrow Cells, pubmed-meshheading:21673072-Cell Proliferation, pubmed-meshheading:21673072-Chromium Radioisotopes, pubmed-meshheading:21673072-Cytokines, pubmed-meshheading:21673072-Female, pubmed-meshheading:21673072-Flow Cytometry, pubmed-meshheading:21673072-Forkhead Transcription Factors, pubmed-meshheading:21673072-Graft vs Host Disease, pubmed-meshheading:21673072-Hematopoiesis, pubmed-meshheading:21673072-Mice, pubmed-meshheading:21673072-Mice, Inbred C57BL, pubmed-meshheading:21673072-Mice, Inbred DBA, pubmed-meshheading:21673072-Receptor, Cannabinoid, CB1, pubmed-meshheading:21673072-Receptor, Cannabinoid, CB2, pubmed-meshheading:21673072-Receptors, Cannabinoid, pubmed-meshheading:21673072-Spleen, pubmed-meshheading:21673072-Splenomegaly, pubmed-meshheading:21673072-T-Lymphocytes, pubmed-meshheading:21673072-Transplantation, Homologous, pubmed-meshheading:21673072-Weight Loss
pubmed:year
2011
pubmed:articleTitle
Targeting cannabinoid receptors as a novel approach in the treatment of graft-versus-host disease: evidence from an experimental murine model.
pubmed:affiliation
Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina 29208, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural