Influence of cytokines tumor necrosis factor-α and interferon-γ on signaling cascades associated with apoptosis in rat PC12 cells

Abstract

During cell-mediated immune response, increased amounts of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) 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-α alone and TNF-α in combination with IFN-γ led to no alteration in cell viability during 48 h of incubation. TNF-α was able to slightly elevate apoptosis compared with cells stimulated with NH2 alone. The combination of TNF-α and IFN-γ 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-α to NH2-stimulated cells resulted in activation of SAPK after 15 min.