Mycoplasma fermentans inhibits tumor necrosis factor alpha-induced apoptosis in the human myelomonocytic U937 cell line.
Mycoplasma fermentans (M. fermentans) was shown to be involved in the alteration of several eukaryotic cell functions (i.e. cytokine production, gene expression), and was suggested as a causative agent in arthritic diseases involving impaired apoptosis. We investigated whether M. fermentans has a pathogenic potential by affecting tumor necrosis factor (TNF)alpha-induced apoptosis in the human myelomonocytic U937 cell line. A significant reduction in the TNFalpha-induced apoptosis (approximately 60%) was demonstrated upon either infection with live M. fermentans or by stimulation with non-live M. fermentans. To investigate the mechanism of M. fermentans antiapoptotic effect, the reduction of mitochondrial transmembrane potential (DeltaPsim) and the protease activity of caspase-8 were measured. In the infected cells, the reduction of DeltaPsim was inhibited (approximately 75%), and an approximately 60% reduction of caspase-8 activity was measured. In conclusion, M. fermentans significantly inhibits TNFalpha-induced apoptosis in U937 cells, and its effect is upstream of the mitochondria and upstream of caspase-8.
Faculty of Health Sciences, Department of Microbiology and Immunology, Soroka University Medical Center, Ben-Gurion University, Beer-Sheva, Israel.
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Horowitz
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Horowitz
D017209:Apoptosis; D053181:Caspase 8; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle; D002469:Cell Separation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D008564:Membrane Potentials; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000473:pathology; D009000:Monocytes / Q000382:microbiology / Q000473:pathology; D016858:Mycoplasma fermentans / Q000378:metabolism*; D009336:Necrosis; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D020298:U937 Cells
D014409:Tumor Necrosis Factor-alpha; C505530:CASP8 protein, human; D053181:Caspase 8; D020169:Caspases