Signaling pathways and genes that inhibit pathogen-induced macrophage apoptosis - CREB and NF-κB as key regulators

Jin Mo Park, Florian R. Greten, Athena Wong, Randal J. Westrick, J. Simon C. Arthur, Kinya Otsu, Alexander Hoffmann, Marc Montminy, Michael Karin (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    268 Citations (Scopus)

    Abstract

    Certain microbes evade host innate immunity by killing activated macrophages with the help of virulence factors that target prosurvival pathways. For instance, infection of macrophages with the TLR4-activating bacterium Bacillus anthracis triggers an apoptotic response due to inhibition of p38 MAP kinase activation by the bacterial-produced lethal toxin. Other pathogens induce macrophage apoptosis by preventing activation of NF-κB, which depends on IκB kinase β (IKKβ). To better understand how p38 and NF-κB maintain macrophage survival, we searched for target genes whose products prevent TLR4-induced apoptosis and a p38-dependent transcription factor required for their induction. Here we describe key roles for transcription factor CREB, a target for p38 signaling, and the plasminogen activator 2 (PAI-2) gene, a target for CREB, in maintenance of macrophage survival.

    Original languageEnglish
    Pages (from-to)319-329
    Number of pages11
    JournalImmunity
    Volume23
    Issue number3
    DOIs
    Publication statusPublished - Sept 2005

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology
    • Infectious Diseases

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