Secretion of interleukin-6 (IL-6) by human monocytes stimulated by muramyl dipeptide and tumour necrosis factor alpha.
We studied IL-6 gene expression in human monocytes stimulated by muramyl dipeptide (MDP), a synthetic immunomodulator derived from mycobacterial cell walls. In control monocytes, two IL-6 transcripts of 3.4 kb and 1.6 kb were easily detected at 2.5 hr of culture and remained stable until 18 hr. In MDP-treated monocytes, three IL-6 RNA species displayed different kinetics of accumulation: a 3.4 kb RNA whose expression already reached its maximum after 2.5 hr exposure to MDP; a 1.6 kb RNA whose expression peaked at 5 hr; and a new RNA species of 1.4 kb which was transiently induced in early time of cell stimulation. TNF-alpha co-operated with MDP to increase IL-6 gene expression and secretion of biological active protein (measured by the hybridoma plasmacytoma growth factor assay). MDP exhibits a broad spectrum of immunomodulation properties such as adjuvant activity, enhancement of macrophage cytotoxicity against tumour and induction of non-specific resistance to intracellular agents. The results reported here suggest that these properties might be linked to the stimulation by MDP of genes coding for key cytokines such as IL-6, TNF and IL-1.
Unité 196 INSERM, Institut Curie, Paris, France.
J
J
Sancéau
R
R
Falcoff
F
F
Beranger
D B
DB
Carter
J
J
Wietzerbin
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology*; D015152:Blotting, Northern; D002478:Cells, Cultured; D004357:Drug Synergism; D015870:Gene Expression / Q000276:immunology*; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis / Q000235:genetics*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D012313:RNA / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D012313:RNA