The C/EBPβ Isoform 34-kDa LAP Is Responsible for NF-IL-6-Mediated Gene Induction in Activated Macrophages, but Is Not Essential for Intracellular Bacteria Killing
In: The Journal of Immunology, Jg. 179 (2007-10-15), S. 5378-5386
Online
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Zugriff:
The C/ebpb gene is translated into three different protein isoforms, two transcriptional activating proteins (38-kDa Full and 34-kDa liver-enriched transcriptional activation protein (LAP)) and one transcriptional inhibitory protein, by alternative use of different AUG initiation codons within the same open reading frame. The isoform 34-kDa LAP is thought to be the most transcriptionally active form of C/EBPβ in macrophages. To assess the function of the 34-kDa LAP in vivo, we generated knock-in mice, in which methionine 20 of C/EBPβ, the start site for the 34-kDa LAP is replaced with an alanine. The expression of the 34-kDa LAP was abolished in C/ebpbM20A/M20A mice. The induction of C/EBPβ target genes, such as inflammatory cytokines, chemokines, prostanoid synthetase, and antimicrobial peptides, was abolished in C/ebpbM20A/M20A macrophages, and C/ebpbM20A/M20A mice were susceptible to Listeria monocytogenes infection. Furthermore, the heat-killed Propionibacterium acnes-induced Th1 response, granuloma formation, and LPS shock were severely impaired. Nevertheless, impairment of intracellular bacteria killing, which is the most prominent phenotype in C/EBPβ-deficient mice, was not observed in C/ebpbM20A/M20A mice. Collectively, we demonstrated that 34-kDa LAP is responsible for NF-IL6-mediated gene induction, but not essential for intracellular bacteria killing in activated macrophages.
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The C/EBPβ Isoform 34-kDa LAP Is Responsible for NF-IL-6-Mediated Gene Induction in Activated Macrophages, but Is Not Essential for Intracellular Bacteria Killing
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Autor/in / Beteiligte Person: | Kaisho, Tsuneyasu ; Yamakami, Megumi ; Omori, Hiroko ; Matsumoto, Makoto ; Akira, Shizuo ; Yamamoto, Masahiro ; Yoshimori, Tamotsu ; Tanaka, Takashi ; Uematsu, Satoshi |
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Zeitschrift: | The Journal of Immunology, Jg. 179 (2007-10-15), S. 5378-5386 |
Veröffentlichung: | The American Association of Immunologists, 2007 |
Medientyp: | unknown |
ISSN: | 1550-6606 (print) ; 0022-1767 (print) |
DOI: | 10.4049/jimmunol.179.8.5378 |
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