IL-1beta acts in synergy with endogenous IL-1beta in A375-S2 human melanoma cell apoptosis through mitochondrial pathway.
Interleukin-1beta (IL-1beta) is a pivotal proinflammatory cytokine. To investigate the mechanism of IL-1beta-induced cell death in human malignant melanoma A375-S2 cells, MTT assay, photomicroscopical observation, DNA agarose gel electrophoresis, radioimmunoassay and Western blot analysis were carried out. IL-1beta did not only induce nuclear condensation and DNA fragmentation, but also increased degradation of two substrates of caspase-3, poly ADP-ribose polymerase (PARP) and inhibitor of caspase-activated DNase (ICAD). Simultaneously, release of precursor of IL-1beta (pro-IL-1beta) and endogenous IL-1beta production were involved in the apoptotic process. IL-1beta enhanced the ratio of Bax/Bcl-2 and Bax/Bcl-xL expression and up-regulated apoptosis inducing factor (AIF) expression, which required the activation of downstream caspases. These results suggest that IL-1beta induces endogenous IL-1beta production, enhances cleavage of caspase downstream substrates and promotes mitochondria mediated apoptosis in A375-S2 cells.
Wang
Che
C
China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, China.
Wang
Min-wei
MW
Tashiro
Shin-ichi
S
Onodera
Satoshi
S
Ikejima
Takashi
T
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020170:Caspase 1 / Q000378:metabolism; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D003851:Deoxyribonucleases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000494:pharmacology* / Q000502:physiology; D015850:Interleukin-6 / Q000494:pharmacology; D008233:Lymphotoxin-alpha / Q000494:pharmacology; D008545:Melanoma / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008928:Mitochondria / Q000502:physiology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D013997:Time Factors
D007375:Interleukin-1; D015850:Interleukin-6; D008233:Lymphotoxin-alpha; D019253:Proto-Oncogene Proteins c-bcl-2; D011065:Poly(ADP-ribose) Polymerases; D003851:Deoxyribonucleases; C109663:caspase-activated deoxyribonuclease; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D020170:Caspase 1