Increased susceptibility to tumor necrosis factor-alpha in butyric acid-induced apoptosis is caused by downregulation of cFLIP expression in Jurkat T cells.
Butyric acid is one of the major extracellular metabolites of periodontopathic Gram-negative bacteria. We previously demonstrated that butyric acid induced apoptosis in human T cells. In the present study, we examined the interaction between butyric acid and TNF-alpha in Jurkat T-cell apoptosis. Simultaneous treatment with TNF-alpha enhanced butyric acid-induced apoptosis by promoting caspase activity more than was achieved by either reagent alone. We examined which genes were associated with the increased susceptibility to TNF-alpha caused by butyric acid, and revealed that expression of cFLIP decreased with increased concentrations of butyric acid. Furthermore, exogenous expression of cFLIP protein suppressed the enhancing effect by TNF-alpha in the apoptosis. These results suggest that butyric acid downregulates cFLIP expression and increases the susceptibility to TNF-alpha by activating caspases via the death receptor signal.
Seto
Shintaro
S
Division of Microbiology, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, Saitama, Japan.
Kurita-Ochiai
Tomoko
T
Ochiai
Kuniyasu
K
D017209:Apoptosis; D020148:Butyric Acid / Q000633:toxicity*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000096:biosynthesis*; D015536:Down-Regulation; D020869:Gene Expression Profiling; D006801:Humans; D019169:Jurkat Cells; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D014409:Tumor Necrosis Factor-alpha; D020148:Butyric Acid