Monocytes stimulated with group B streptococci or interferons release tumour necrosis factor-related apoptosis-inducing ligand.
Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a cytotoxic member of the TNF family. Some reports have shown that TRAIL is released from cells in a soluble form. In this work, we have investigated the mechanism of release of TRAIL from monocytes. First, we show that whole gram-positive, gram-negative and mycoplasmal bacteria as well as lipopolysaccharide (LPS), interferon-alpha (IFN-alpha), -beta and -gamma all induced upregulation of TRAIL on the surface of human monocytes. Next, we show that IFN-alpha, -beta and -gamma all induced a dose-dependent release of TRAIL, giving significant amounts of soluble TRAIL after 2 days. Of the bacteria, only the Group B streptococcus COH-1 (GBS) induced release of TRAIL and concomittantly induced IFN-alpha. Monocytes stimulated with GBS or IFN-alpha also showed extensive cell death. When monocyte apoptosis was prevented by interleukin-1, GM-CSF, LPS or the caspase inhibitor zVADfmk, the IFN-alpha-induced release of TRAIL was reduced, whereas agents inducing necrosis caused increased release of TRAIL. LPS also prevented release of TRAIL from GBS-stimulated monocytes. The release of TRAIL from IFN-alpha-stimulated monocytes was reduced by inhibitors of both cysteine and metalloproteases. We conclude that bacteria and IFN induce upregulation of membrane TRAIL and that release of TRAIL is associated with cell death.
Halaas
Ø
Ø
Institute of Cancer Research and Molecular Biology, NTNU, N-7489 Trondheim, Norway. oyvind.halaas@medisin.ntnu.no
Liabakk
N-B
NB
Vik
R
R
Beninati
C
C
Henneke
P
P
Sundan
A
A
Espevik
T
T
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology; D051017:Apoptosis Regulatory Proteins; D003601:Cytotoxicity Tests, Immunologic; D005434:Flow Cytometry; D006801:Humans; D007372:Interferons / Q000276:immunology*; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007976:Leupeptins / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology*; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology; D011480:Protease Inhibitors / Q000494:pharmacology; D013292:Streptococcus agalactiae / Q000276:immunology*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D015854:Up-Regulation
D000590:Amino Acid Chloromethyl Ketones; D051017:Apoptosis Regulatory Proteins; D007976:Leupeptins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011480:Protease Inhibitors; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D007372:Interferons; D007930:Leucine; C032854:leupeptin; C024974:E 64