Mechanisms underlying the suppression of inflammatory responses in peritoneal macrophages of middle-aged mice

Ken Shirato*, Kazuhiko Imaizumi

*Corresponding author for this work

    Research output: Chapter in Book/Report/Conference proceedingChapter

    2 Citations (Scopus)


    We investigated the molecular mechanisms underlying the deterioration of macrophage inflammatory responses in middle-aged mice, focusing on the agerelated reduction in protein synthesis rate. Peritoneal macrophages were isolated from male BALB/c mice aged 2 months (young) and 12 months (middle-aged), and stimulated with lipopolysaccharide (LPS). At the protein level, LPS-stimulated proinflammatory cytokine release and intracellular accumulation of bactericidal mediators from macrophages were clearly lower in middle-aged mice than in young mice. However, LPS caused a marked increase in the mRNA expression of these genes in the macrophages of both young and middle-aged mice. Moreover, LPS induced comparable phosphorylation levels of signaling proteins downstream of toll-like receptor (TLR) in young and middle-aged mice. In contrast, levels of the inactive (phosphorylated) form of eukaryotic initiation factor 2α (eIF-2α) were higher in macrophages from middle-aged mice than in macrophages from young mice. Suppression of the LPS-stimulated inflammatory responses observed in middleaged mice could be mimicked by treating the murine macrophage RAW264.7 cells with salubrinal, an inhibitor of the phosphatase that dephosphorylates eIF-2α. In conclusion, post-transcriptional suppression of macrophage inflammatory responses during middle age requires phosphorylation of eIF-2α.

    Original languageEnglish
    Title of host publicationPhysical Activity, Exercise, Sedentary Behavior and Health
    PublisherSpringer Japan
    Number of pages10
    ISBN (Print)9784431553335, 9784431553328
    Publication statusPublished - 2015 Jan 1


    • Aging
    • Eukaryotic initiation factor
    • Inflammatory response
    • Middle-aged mice
    • Peritoneal macrophages

    ASJC Scopus subject areas

    • Medicine(all)
    • Engineering(all)


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