The PI3 kinase, p38 SAP kinase, and NF-κB signal transduction pathways are involved in the survival and maturation of lipopolysaccharide-stimulated human monocyte–derived dendritic cells

Abstract

As a dendritic cell (DC) matures, it becomes more potent as an antigen-presenting cell. This functional change is accompanied by a change in DC immunophenotype. The signal transduction events underlying this process are poorly characterized. In this study, we have investigated the signal transduction pathways involved in the lipopolysaccharide (LPS)-induced maturation of human monocyte–derived DCs (MoDCs) in vitro. We show that exposure of immature MoDCs to LPS activates the p38 stress-activated protein kinase (p38SAPK), extracellular signal–regulated protein kinase (ERK), phosphoinositide 3-OH kinase (PI3 kinase)/Akt, and nuclear factor (NF)-κB pathways. Studies using inhibitors demonstrate that PI3 kinase/Akt but not the other pathways are important in maintaining survival of LPS-stimulated MoDCs. Inhibiting p38SAPK prevented activation of the transcription factors ATF-2 and CREB and significantly reduced the LPS-induced up-regulation of CD80, CD83, and CD86, but did not have any significant effect on the LPS-induced changes in macropinocytosis or HLA-DR, CD40, and CD1a expression. Inhibiting the NF-κB pathway significantly reduced the LPS-induced up-regulation of HLA-DR as well as CD80, CD83, and CD86. Inhibiting the p38SAPK and NF-κB pathways simultaneously had variable effects depending on the cell surface marker studied. It thus appears that different aspects of LPS-induced MoDC maturation are regulated by different and sometimes overlapping pathways.

Efficient Inhibition of Wear‐Debris‐Induced Osteolysis by Surface Biomimetic Engineering of Titanium Implant with a Mussel‐Derived Integrin‐Targeting Peptide

“…Previous studies have established that NF‐κB signaling mediates RANKL‐induced osteoclastogenesis,[12c,21] and the activation of NF‐κB can be regulated by PI3K/AKT . Moreover, the activations of NF‐κB and PI3K/AKT relate to the transference of P65 (a NF‐κB subunit) from the cytoplasm to the nucleus .…”

Salvianolic acid B suppresses maturation of human monocyte-derived dendritic cells by activating PPARγ

“…Next, we analysed the effect of Sal B on TLR4/MyD88‐mediated MAPK pathway during h‐monDC maturation (Ardeshna et al ., 2000; Arrighi et al ., 2001). As shown in Figure 2C, Sal B (50 µM) reduced ox‐LDL‐induced activation of p38 and JNK1/2, and ox‐LDL‐induced activation of p38 and JNK1/2 was also inhibited by SB203580 (a specific p38‐MAPK blocker) or SP600125 (a specific JNK1/2 blocker).…”

“…TLR4‐mediated maturation of h‐monDC is regulated by different signal transduction pathways, including PI3 kinase, p38MAPkinase and NF‐kB (Ardeshna et al ., 2000). LPS‐induced up‐regulation of TLR4 could activate all three MAPK cascades.…”

Daphnetin Alleviates Experimental Autoimmune Encephalomyelitis via Regulating Dendritic Cell Activity

“…These changes enable DCs migrate to the secondary lymphoid organs where they efficiently promote T‐cell responses . It has been demonstrated that some intracellular signaling pathways, such as NF‐ κ B and mitogen‐activated protein kinases (MAPKs), are involved in DCs’ activation and maturation . NF‐ κ B is a ubiquitous transcription factor that controls a variety of biological processes such as immunity, inflammation, tumorigenesis, and cellular growth and survival.…”