Influence of cytokines tumor necrosis factor-alpha and interferon-gamma on signaling cascades associated with apoptosis in rat PC12 cells.
During cell-mediated immune response, increased amounts of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) are released. In the present study, we investigated the potential of these two cytokines to mediate apoptosis and to alter signal transduction pathways involved in undifferentiated PC12 cells. To induce apoptosis, the pteridine 7,8-dihydroneopterin (NH2) was used. TNF-alpha alone and TNF-alpha in combination with IFN-gamma led to no alteration in cell viability during 48 h of incubation. TNF-alpha was able to slightly elevate apoptosis compared with cells stimulated with NH2 alone. The combination of TNF-alpha and IFN-gamma almost completely abrogated the rate of apoptosis induced by NH2. Similar degrees of activation of extracellular protein kinase were found after the addition of cytokines or cytokines in combination with NH2. Stress-activated protein kinase (SAPK) was not activated by the cytokines alone, whereas adding the cytokine TNF-alpha to NH2-stimulated cells resulted in activation of SAPK after 15 min.
Enzinger
C
C
Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Fritz-Pregl Strasse 3, 6020 Innsbruck, Austria.
Wirleitner
B
B
Böck
G
G
Baier-Bitterlich
G
G
Fuchs
D
D
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D007111:Immunity, Cellular / Q000187:drug effects / Q000502:physiology; D007371:Interferon-gamma / Q000378:metabolism* / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D019798:Neopterin / Q000378:metabolism / Q000031:analogs & derivatives; D019636:Neurodegenerative Diseases / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000276:immunology / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D016716:PC12 Cells; D011621:Pteridines / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
D000975:Antioxidants; D011621:Pteridines; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C000976:7,8-dihydroneopterin; D019798:Neopterin; D007371:Interferon-gamma; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases