In vitro TNF-alpha production and in vivo alteration of TNF-alpha RNA in mouse peritoneal macrophages after treatment with different bacterial derived agents.
Since muramyl dipeptide (MDP) was recognized as a potent monocyte/macrophage activating agent, many MDP analogues were synthesized and tested for their ability to augment the host immune defence system against neoplasms. This study was performed to determine whether the newly synthesized desmuramyl N-acyl dipeptides LK 409 and LK 410 were also capable of affecting the immune system. For this purpose, the peritoneal macrophages were incubated in vitro with these two agents and TNF-alpha production was measured. In addition, the effect of LK 409 and LK 410 on TNF-alpha and IL-1 RNA levels in in vivo stimulated macrophages was determined by quantitative polymerase chain reaction (RT-PCR). None of the LK 409 and LK 410 concentrations tested were able to render macrophages in vitro to excrete a detectable amount of TNF-alpha in the supernatant fluid. However, the TNF-alpha and IL-1 RNA levels in macrophages of in vivo treated mice (C57Bl/6) were increased in comparison to mock-treated mice. The results indicate that LK 409 and LK 410 are capable of inducing an increase in TNF-alpha and IL-1 RNA levels, yet in vitro TNF-alpha production remains under detectable levels (40 U/ml).
Novaković
S
S
Department of Tumor Biology and Biotherapy, Institute of Oncology, Ljubljana, Slovenia.
Boldogh
I
I
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D004151:Dipeptides / Q000494:pharmacology*; D005260:Female; D007375:Interleukin-1 / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012313:RNA / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D004151:Dipeptides; D007375:Interleukin-1; C079179:LK 409; C079180:LK 410; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D012313:RNA