Anti-(tumor necrosis factor) alters the response of human monocytes to liposomal muramyl tripeptide.
The purpose of this study was to examine the mechanisms by which liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) stimulates monocytes to produce tumor necrosis factor (TNF) and interleukin-1 (IL-1). We have previously shown that secretion of TNF protein occurred 2-4 h following incubation of monocytes with L-MTP-PE and that this stimulation of TNF production was associated with an increase in TNF mRNA. Increased intracellular interleukin-1 alpha (IL-1 alpha) and IL-1 beta were not detected until 8 h after exposure to L-MTP-PE. To determine whether TNF played a role in the stimulation of IL-1 production by L-MTP-PE, normal human monocytes were incubated with L-MTP-PE or medium in the presence or absence of anti-TNF or anti IL-1 alpha plus anti IL-1 beta. Enhanced expression of IL-1 alpha and IL-1 beta mRNA was inhibited at 4 h but not 24 h when monocytes were incubated with L-MTP-PE plus anti-TNF compared with L-MTP-PE alone. By contrast, enhanced expression of TNF mRNA was not inhibited at any time when monocytes were incubated with L-MTP-PE and anti-IL-1 alpha plus anti-IL-1 beta. These data indicate that the up-regulation of IL-1 seen in monocytes following L-MTP-PE exposure may be due in part to the production of TNF. The up-regulation of TNF, however, appears to be independent of IL-1 production.
Maeda
M
M
Department of Cell Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Asano
T
T
Kleinerman
E S
ES
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004337:Drug Carriers; D005786:Gene Expression Regulation; D006801:Humans; D015151:Immunoblotting; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D008081:Liposomes; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D004337:Drug Carriers; D007375:Interleukin-1; D008081:Liposomes; D010714:Phosphatidylethanolamines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C037144:mifamurtide; D000119:Acetylmuramyl-Alanyl-Isoglutamine