Liposome-encapsulated muramyl tripeptide up-regulates monocyte chemotactic and activating factor gene expression in human monocytes at the transcriptional and post-transcriptional levels.
Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) is a novel immune modulator that is now under investigation against metastatic melanoma and osteosarcoma. We have already reported that L-MTP-PE induced monocyte-mediated tumoricidal activity and up-regulation of the tumor necrosis factor and interleukin-1 (IL-1) in vivo and in vitro. We now demonstrate that L-MTP-PE also induces monocyte chemotactic and activating factor (MCAF) mRNA expression at both the transcriptional and post-transcriptional levels. Monocyte chemotactic activity was also present in the supernatants of L-MTP-PE-stimulated cells. In monocytes, the increased expression of MCAF was induced rapidly (by 2 h) but was short-lived. By 4 h, MCAF mRNA had decreased to background level. We found no change in MCAF mRNA levels in lymphocytes exposed to L-MTP-PE. We therefore conclude that L-MTP-PE selectively up-regulates MCAF expression in monocytes and that MCAF may play a role in the tumoricidal and immune-stimulating activity of L-MTP-PE.
Asano
T
T
Department of Cell Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Matsushima
K
K
Kleinerman
E S
ES
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015152:Blotting, Northern; D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000096:biosynthesis* / Q000235:genetics; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D006207:Half-Life; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008081:Liposomes; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis / Q000187:drug effects; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*; D015854:Up-Regulation
D000970:Antineoplastic Agents; D018932:Chemokine CCL2; D002630:Chemotactic Factors; D016207:Cytokines; D004337:Drug Carriers; D016209:Interleukin-8; D008081:Liposomes; D010714:Phosphatidylethanolamines; D012333:RNA, Messenger; C037144:mifamurtide; D000119:Acetylmuramyl-Alanyl-Isoglutamine