Gene expression reprogramming protects macrophage from septic-induced cell death

Edielle Sant Anna Melo, Denise F. Barbeiro, Renata Gorjão, Ester Correia Sarmento Rios, Dewton Vasconcelos, Irineu T. Velasco, Csaba Szabo, Rui Curi, Thais Martins De Lima-Salgado, Francisco Garcia Soriano

    Research output: Contribution to journalArticle

    20 Scopus citations

    Abstract

    Sepsis induces a systemic inflammatory response leading to tissue damage and cell death. LPS tolerance affects inflammatory response. To comprehend potential new mechanisms of immune regulation in endotoxemia, we examined macrophage mRNA expression by macroarray affected by LPS tolerance. LPS tolerance was induced with subcutaneous administration of 1. mg/kg/day of LPS over 5 days. Macrophages were isolated from the spleen and the expression of 1200 genes was quantitatively analyzed by the macroarray technique. The tolerant group displayed relevant changes in the expression of 84 mRNA when compared to naïve mice. A functional group of genes related to cell death regulation was identified. PARP-1, caspase 3, FASL and TRAIL genes were confirmed by RT-PCR to present lower expression in tolerant mice. In addition, reduced expression of the pro-inflammatory genes TNF-α and IFN-γ in the tolerant group was demonstrated. Following this, animals were challenged with polymicrobial sepsis. Flow cytometry analysis showed reduced necrosis and apoptosis in macrophages from the tolerant group compared to the naïve group. Finally, a survival study showed a significant reduction in mortality in the tolerant group. Thus, in the current study we provide evidence for the selective reprogramming of the gene expression of cell death pathways during LPS tolerance and link these changes to protection from cell death and enhanced survival rates.

    Original languageEnglish (US)
    Pages (from-to)2587-2593
    Number of pages7
    JournalMolecular Immunology
    Volume47
    Issue number16
    DOIs
    StatePublished - Oct 1 2010

    Keywords

    • Apoptosis
    • Gene expression
    • Immunoparalysia
    • Macrophage
    • Necrosis
    • Sepsis

    ASJC Scopus subject areas

    • Immunology
    • Molecular Biology

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  • Cite this

    Melo, E. S. A., Barbeiro, D. F., Gorjão, R., Rios, E. C. S., Vasconcelos, D., Velasco, I. T., Szabo, C., Curi, R., De Lima-Salgado, T. M., & Soriano, F. G. (2010). Gene expression reprogramming protects macrophage from septic-induced cell death. Molecular Immunology, 47(16), 2587-2593. https://doi.org/10.1016/j.molimm.2010.06.011