SLE serum induces classical caspase-dependent apoptosis independent of death receptors.
The main source of autoantigens in systemic lupus erythematosus (SLE) is most likely apoptotic material. We have previously shown that sera from SLE patients can induce apoptosis in monocytes and lymphocytes, and here we characterized mechanisms of apoptosis induced by SLE serum. SLE serum seems to induce caspase-dependent classical apoptosis since cells exposed to SLE serum displayed morphology consistent with classical apoptosis as demonstrated by confocal microscopy, and pan-caspase inhibitor Z-VAD.fmk significantly reduced SLE serum-induced apoptosis. Death-receptor-independent pathways seemed to be involved since SLE serum induced apoptosis equally in FADD-mutant and wild-type Jurkat cell lines, and blocking of Fas and TNFR1 did not reduce apoptosis induction. Importantly, apoptosis was significantly reduced in a Bcl-2 overexpressing Jurkat cell line indicating involvement of mitochondrial pathways. Thus, based on morphology and caspase inhibition experiments, we have demonstrated that SLE serum induce classical caspase-dependent apoptosis, and this was independent of death receptor pathways.
Department of Rheumatology, Lund University Hospital, SE-221 85, Lund, Sweden. Anders.Bengtsson@med.lu.se
Anders A
AA
Bengtsson
Birgitta
B
Gullstrand
Lennart
L
Truedsson
Gunnar
G
Sturfelt
D017209:Apoptosis; D001324:Autoantigens; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000276:immunology; D008928:Mitochondria / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D053218:Receptors, Death Domain / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D019014:fas Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism
D001324:Autoantigens; D061945:Caspase Inhibitors; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D053218:Receptors, Death Domain; D047888:Receptors, Tumor Necrosis Factor, Type I; D019014:fas Receptor; D020169:Caspases