Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2001-1-4
pubmed:abstractText
Product R (Reticulose(TM)) is a peptide-nucleic acid immunomodulator with broad-spectrum antiviral activity that was recently shown to increase expression of mRNAs encoding the proinflammatory cytokines, IFN-gamma, IL-1beta, IL-6 and TNF-alpha. Since these cytokines induce expression of the chemokines, MIP-1alpha, MIP-1beta, RANTES, and SDF-1, all of which inhibit viral infectivity, we were interested to determine if Product R also alters chemokine expression. In addition, the finding, that Product R decreases HIV-1 RNA and extracellular p24 antigen in H9 T-lymphoma cells, suggested to us that this drug may block viral infection by reducing the expression of chemokine receptors on target cells. We have therefore utilized H9 cells to test the effects of Product R on expression of mRNAs encoding the chemokine receptors, CD4, CXCR4 and CCR5, as well as their ligands, IL-16, SDF-1, MIP-1alpha, MIP-1beta, and RANTES, by RT-PCR. We also assayed the effect of Product R on surface receptor expression by flow cytometry, and on the chemotactic activity of these cells towards the CXCR4 ligand, SDF-1, and the CCR5 ligands, MIP-1alpha and RANTES. H9 cells were cultured for 3-21 days in medium containing 5% or 10% Product R, or 5% or 10% PBS. We found that, compared to control cultures, cells cultured in media containing Product R expressed lower amounts of CXCR4 and CCR5 mRNA and surface antigen at all time points. Culture for 3 days in media containing Product R also reduced the ability of cells to migrate towards 10-20 ng/ml SDF-1 and 100-250 ng/ml RANTES. In contrast, Product R had no effect on the expression of CD4 mRNA and receptor protein, or on expression of IL-16 mRNA. These findings suggest that Product R may have clinical efficacy in HIV-1-infected patients by downregulating viral coreceptors on target T-cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Adjuvants, Immunologic, http://linkedlifedata.com/resource/pubmed/chemical/Anti-HIV Agents, http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD4, http://linkedlifedata.com/resource/pubmed/chemical/CXCL12 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL3, http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL4, http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL5, http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CXCL12, http://linkedlifedata.com/resource/pubmed/chemical/Chemokines, CXC, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-16, http://linkedlifedata.com/resource/pubmed/chemical/Macrophage Inflammatory Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Peptide Nucleic Acids, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Neoplasm, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, CCR5, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, CXCR4, http://linkedlifedata.com/resource/pubmed/chemical/reticulose
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0165-2478
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
74
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
189-95
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:11064099-Adjuvants, Immunologic, pubmed-meshheading:11064099-Anti-HIV Agents, pubmed-meshheading:11064099-Antigens, CD4, pubmed-meshheading:11064099-Chemokine CCL3, pubmed-meshheading:11064099-Chemokine CCL4, pubmed-meshheading:11064099-Chemokine CCL5, pubmed-meshheading:11064099-Chemokine CXCL12, pubmed-meshheading:11064099-Chemokines, CXC, pubmed-meshheading:11064099-Chemotaxis, Leukocyte, pubmed-meshheading:11064099-Down-Regulation, pubmed-meshheading:11064099-Flow Cytometry, pubmed-meshheading:11064099-Gene Expression Regulation, Neoplastic, pubmed-meshheading:11064099-Humans, pubmed-meshheading:11064099-Interleukin-16, pubmed-meshheading:11064099-Lymphoma, T-Cell, pubmed-meshheading:11064099-Macrophage Inflammatory Proteins, pubmed-meshheading:11064099-Neoplasm Proteins, pubmed-meshheading:11064099-Peptide Nucleic Acids, pubmed-meshheading:11064099-RNA, Messenger, pubmed-meshheading:11064099-RNA, Neoplasm, pubmed-meshheading:11064099-Receptors, CCR5, pubmed-meshheading:11064099-Receptors, CXCR4, pubmed-meshheading:11064099-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:11064099-T-Lymphocytes, pubmed-meshheading:11064099-Tumor Cells, Cultured
pubmed:year
2000
pubmed:articleTitle
CXCR4 and CCR5 expression by H9 T-cells is downregulated by a peptide-nucleic acid immunomodulator.
pubmed:affiliation
Laboratory of Immunology, Advanced Viral Research Institute, Advanced Viral Research Corp., 200 Corporate Boulevard South, Yonkers, NY 10701, USA.
pubmed:publicationType
Journal Article, Comparative Study