Fas ligation induces IL-1beta-dependent maturation and IL-1beta-independent survival of dendritic cells: different roles of ERK and NF-kappaB signaling pathways.
The mechanisms that underpin the intriguing capacity of Fas ligation on dendritic cells (DCs) to induce maturation and activation, rather than apoptosis, remain unclear. In the present study we confirm that Fas signaling induces both phenotypic and functional maturation of murine DCs, and we demonstrate that phenotypic maturation is associated with phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, activation of caspase-1, and secretion of interleukin-beta (IL-1beta). Specific inhibition of ERK1/2 diminished Fas ligation-induced caspase-1 activation, IL-1beta secretion, and ensuing up-regulation of developmental markers, whereas treatment with neutralizing anti-IL-1beta antibody abrogated phenotypic and functional maturation, indicating that IL-1beta mediates Fas ligation-induced DC maturation in an autocrine manner. NF-kappaB activation was responsible for maintaining DC viability after Fas ligation. Inhibiting NF-kappaB did not affect either IL-1beta secretion or phenotypic maturation but rather sensitized DCs to Fas-mediated apoptosis. In conclusion, positive signals originating from Fas are transduced through at least 2 different intracellular pathways in DCs, promoting not only survival but also an increase in maturation that correlates with increased antigen-presentation capability.
Guo
Zhenhong
Z
Institute of Immunology, Second Military Medical University, 800 Xiangyin Rd, Shanghai 200433, People's Republic of China.
Zhang
Minghui
M
An
Huazhang
H
Chen
Weilin
W
Liu
Shuxun
S
Guo
Jun
J
Yu
Yizhi
Y
Cao
Xuetao
X
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019898:Autocrine Communication; D020170:Caspase 1 / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D025461:Feedback, Physiological; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction; D019014:fas Receptor / Q000502:physiology*
D016207:Cytokines; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D016328:NF-kappa B; D019014:fas Receptor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D020170:Caspase 1