TNF Tolerance in Monocytes and Macrophages: Characteristics and Molecular Mechanisms

Figure 2

Transcriptional repression during low-dose-induced TNF tolerance. In low-dose TNF preincubated cells, p65 phosphorylation of the activating phosphorylation site Ser536 is blocked via direct protein-protein interaction with C/EBPβ. In addition, an increased phosphorylation of the inhibitory site p65-Ser468 can be observed. Both events may be influenced by GSK3 and negatively regulate the transcription of immunologically relevant genes in low-dose TNF-tolerant cells.