Recently we demonstrated that the ability of tumor necrosis factor ␣ (TNF␣) to stimulate the human cytomegalovirus (HCMV) IE1/2 enhancer/promoter activity in myeloid progenitor-like cells decreases when these cells differentiate into promonocytic cells. In addition, TNF␣ stimulation in the progenitor-like cell line HL-60 was shown to be mediated by nuclear factor B (NF-B) activation and its binding to the 18-base pair sequence motifs of the IE1/2 enhancer. We demonstrate here that the cell differentiation-dependent reduction of TNF␣ stimulation is not due to insufficient NF-B activation but correlates with increased synthesis of the monocyte differentiation-associated factors CCAAT/enhancerbinding protein (C/EBP) ␣ and ␤. Several clinical studies have shown that systemic inflammation is a key factor for human cytomegalovirus (HCMV) 1 (re)activation in both immunosuppressed and non-immunosuppressed patients (1-6). The proinflammatory cytokine tumor necrosis factor ␣ (TNF␣) has been identified as a powerful mediator of HCMV stimulation and reactivation in human and murine monocyte/ macrophage progenitor cells (7,8). These are a main target cell for HCMV latency (7, 9 -11). However, TNF␣ did not directly influence reactivation of the virus in peripheral blood mononuclear leukocytes induced by allogenic stimulation (12) 2 suggesting distinct regulatory events in progenitor and mature peripheral blood mononuclear leukocytes.The HCMV IE1/2 enhancer/promoter regulates ie1/2 gene expression and initiation of viral replication (13). Recently, we observed that TNF␣ strongly activates in vitro HCMV IE1/2 enhancer/promoter in the undifferentiated granulocyte/macrophage progenitor-like cell line HL-60 (5, 14, 15). The stimulatory effect of TNF␣ on the IE1/2 promoter decreased as myeloid progenitor cells differentiated into (pro-)monocytic cells. In U937 and THP-1 cells (representing the phenotype of promonocytes and mature monocytes, respectively), the stimulatory effect of TNF␣ was reduced by about 70% and was completely abrogated, respectively, compared with HL-60 cells (14). Differentiation of HL-60 cells also diminished the TNF␣ effect on the IE1/2 enhancer/promoter (14).The stimulatory effect of TNF␣ on the IE1/2 enhancer/promoter in undifferentiated HL-60 cells is mediated via binding to its p55 type I receptor and subsequent activation of NF-B heterodimer p65/p50 that binds in the nucleus to the 18-bp repetitive sequence motifs in the IE1/2 enhancer (5, 15). Interestingly, this TNF␣-induced signal transduction pathway was also identified in U937 and THP-1 cells indicating that the observed differentiation-dependent changes in TNF␣-mediated regulation of the HCMV IE1/2 enhancer/promoter cannot be explained by decreased activation of NF-B p65/p50.The C/EBP family of transcription factors together with AP-1

Three-dimensional soft tissue prediction employing finite element modeling is a useful aid for implementing esthetically-optimized treatment planning.