Cells induced to undergo apo in the presence of the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone stimulate Mo derived phagocytes to secrete proinflammatory cytokines.
In contrast to nec, the apo is not accompanied by local inflammation. The immunosuppressive effects of apo cells have been repeatedly reported and a dysregulation of apo is discussed to play a major role in the pathogenesis of autoimmune disorders. The intracellular executioners of apo are the cysteine-aspartic acid proteases, also known as caspases that cleave a variety of intracellular substrates and mediate the morphological changes observed during apo. The association of autoimmune diseases with defects in caspase function indicates the necessity for functional integrity of caspases in the apo cell death machinery. Here, we describe that cells undergoing apo in presence of the pancaspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone stimulated MPhi to secrete proinflammatory cytokines. These findings indicate that caspase signalling is of central importance for silent and non- or anti-inflammatory cell death.
Heyder
Petra
P
Department of Medicine V, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany. petra.heyder@med.uni-heidelberg.de
Bekeredjian-Ding
Isabelle
I
Krienke
Stefan
S
Lorenz
Hanns-Martin
HM
Schiller
Martin
M
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D061945:Caspase Inhibitors; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D016207:Cytokines; D004791:Enzyme Inhibitors; C426824:benzyloxycarbonyl-valyl-alanyl-(methyl)aspartic acid fluoromethyl ketone