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 Citations (Scopus)

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 2010
Externally publishedYes

Fingerprint

Cell Death
Macrophages
Gene Expression
Sepsis
Genes
Messenger RNA
Endotoxemia
Caspase 3
Flow Cytometry
Necrosis
Spleen
Survival Rate
Apoptosis
Polymerase Chain Reaction
Mortality

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology

Cite this

Melo, E. S. A., Barbeiro, D. F., Gorjão, R., Rios, E. C. S., Vasconcelos, D., Velasco, I. T., ... 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

Gene expression reprogramming protects macrophage from septic-induced cell death. / Melo, Edielle Sant Anna; Barbeiro, Denise F.; Gorjão, Renata; Rios, Ester Correia Sarmento; Vasconcelos, Dewton; Velasco, Irineu T.; Szabo, Csaba; Curi, Rui; De Lima-Salgado, Thais Martins; Soriano, Francisco Garcia.

In: Molecular Immunology, Vol. 47, No. 16, 10.2010, p. 2587-2593.

Research output: Contribution to journalArticle

Melo, ESA, Barbeiro, DF, Gorjão, R, Rios, ECS, Vasconcelos, D, Velasco, IT, Szabo, C, Curi, R, De Lima-Salgado, TM & Soriano, FG 2010, 'Gene expression reprogramming protects macrophage from septic-induced cell death', Molecular Immunology, vol. 47, no. 16, pp. 2587-2593. https://doi.org/10.1016/j.molimm.2010.06.011
Melo ESA, Barbeiro DF, Gorjão R, Rios ECS, Vasconcelos D, Velasco IT et al. Gene expression reprogramming protects macrophage from septic-induced cell death. Molecular Immunology. 2010 Oct;47(16):2587-2593. https://doi.org/10.1016/j.molimm.2010.06.011
Melo, Edielle Sant Anna ; Barbeiro, Denise F. ; Gorjão, Renata ; Rios, Ester Correia Sarmento ; Vasconcelos, Dewton ; Velasco, Irineu T. ; Szabo, Csaba ; Curi, Rui ; De Lima-Salgado, Thais Martins ; Soriano, Francisco Garcia. / Gene expression reprogramming protects macrophage from septic-induced cell death. In: Molecular Immunology. 2010 ; Vol. 47, No. 16. pp. 2587-2593.
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