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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 9
pubmed:dateCreated
2004-8-10
pubmed:abstractText
Z-100 is an arabinomannan extracted from Mycobacterium tuberculosis that has various immunomodulatory activities, such as the induction of interleukin 12, interferon gamma (IFN-gamma) and beta-chemokines. The effects of Z-100 on human immunodeficiency virus type 1 (HIV-1) replication in human monocyte-derived macrophages (MDMs) are investigated in this paper. In MDMs, Z-100 markedly suppressed the replication of not only macrophage-tropic (M-tropic) HIV-1 strain (HIV-1JR-CSF), but also HIV-1 pseudotypes that possessed amphotropic Moloney murine leukemia virus or vesicular stomatitis virus G envelopes. Z-100 was found to inhibit HIV-1 expression, even when added 24 h after infection. In addition, it substantially inhibited the expression of the pNL43lucDeltaenv vector (in which the env gene is defective and the nef gene is replaced with the firefly luciferase gene) when this vector was transfected directly into MDMs. These findings suggest that Z-100 inhibits virus replication, mainly at HIV-1 transcription. However, Z-100 also downregulated expression of the cell surface receptors CD4 and CCR5 in MDMs, suggesting some inhibitory effect on HIV-1 entry. Further experiments revealed that Z-100 induced IFN-beta production in these cells, resulting in induction of the 16-kDa CCAAT/enhancer binding protein (C/EBP) beta transcription factor that represses HIV-1 long terminal repeat transcription. These effects were alleviated by SB 203580, a specific inhibitor of p38 mitogen-activated protein kinases (MAPK), indicating that the p38 MAPK signalling pathway was involved in Z-100-induced repression of HIV-1 replication in MDMs. These findings suggest that Z-100 might be a useful immunomodulator for control of HIV-1 infection.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-1317
pubmed:author
pubmed:issnType
Print
pubmed:volume
85
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2603-13
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15302954-Adjuvants, Immunologic, pubmed-meshheading:15302954-Antigens, CD4, pubmed-meshheading:15302954-Cells, Cultured, pubmed-meshheading:15302954-Dose-Response Relationship, Drug, pubmed-meshheading:15302954-Down-Regulation, pubmed-meshheading:15302954-Gene Deletion, pubmed-meshheading:15302954-Gene Products, env, pubmed-meshheading:15302954-Genes, nef, pubmed-meshheading:15302954-Genetic Vectors, pubmed-meshheading:15302954-HIV-1, pubmed-meshheading:15302954-Humans, pubmed-meshheading:15302954-Interferon-beta, pubmed-meshheading:15302954-Lipids, pubmed-meshheading:15302954-Macrophages, pubmed-meshheading:15302954-Mannans, pubmed-meshheading:15302954-Mycobacterium tuberculosis, pubmed-meshheading:15302954-Receptors, CCR5, pubmed-meshheading:15302954-Transcription, Genetic, pubmed-meshheading:15302954-Transfection, pubmed-meshheading:15302954-Virus Replication
pubmed:year
2004
pubmed:articleTitle
Inhibition of human immunodeficiency virus type 1 replication by Z-100, an immunomodulator extracted from human-type tubercle bacilli, in macrophages.
pubmed:affiliation
Department of Immunotherapeutics, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't