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J. Exp. Med.,
Volume 188, Number 11, December 7, 1998 2175-2180
By
From the * Consiglio Nazionale delle Ricerche Center of Molecular and Cellular Pharmacology and the
Department of Biotechnology and Biological Sciences, Second University of Milano, 20126 Milano,
Italy; and the Although dendritic cell (DC) activation is a critical event for the induction of immune responses,
the signaling pathways involved in this process have not been characterized. In this report, we
show that DC activation induced by lipopolysaccharide (LPS) can be separated into two distinct
processes: first, maturation, leading to upregulation of MHC and costimulatory molecules, and second, rescue from immediate apoptosis after withdrawal of growth factors (survival). Using a DC
culture system that allowed us to propagate immature growth factor-dependent DCs, we have investigated the signaling pathways activated by LPS. We found that LPS induced nuclear translocation of the nuclear factor (NF)- Department of Microbiology and Immunology, University of British Columbia,
Vancouver V6T 1Z3, British Columbia, Canada
B transcription factor. Inhibition of NF-B activation blocked
maturation of DCs in terms of upregulation of major histocompatibility complex and costimulatory molecules. In addition, we found that LPS activated the extracellular signal-regulated kinase
(ERK), and that specific inhibition of MEK1, the kinase which activates ERK, abrogated the ability
of LPS to prevent apoptosis but did not inhibit DC maturation or NF-B nuclear translocation.
These results indicate that ERK and NF-B regulate different aspects of LPS-induced DC activation: ERK regulates DC survival whereas NF-B is responsible for DC maturation.
B
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