Gene expression reprogramming protects macrophage from septic-induced cell death

Autor(es)

Melo, Edielle Sant'Anna ^[1] ; Barbeiro, Denise F. ^[1] ; Gorjao, Renata ^[2] ; Sarmento Rios, Ester Correia ^[1] ; Vasconcelos, Dewton ^[3] ; Velasco, Irineu T. ^[1] ; Szabo, Csaba ^[4] ; Curi, Rui ^[2] ; de Lima-Salgado, Thais Martins ^[1] ; Soriano, Francisco Garcia ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Dept Emergency Med, Sao Paulo - Brazil

^[2] Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo - Brazil

^[3] Inst Trop Med, Lab Invest Dermatol & Immunodeficiency, Dept Dermatol, Sao Paulo - Brazil

^[4] Univ Med & Dent New Jersey, Newark, NJ 07103 - USA

• Tipo de documento: Artigo Científico
• Fonte: Molecular Immunology; v. 47, n. 16, p. 2587-2593, OCT 2010.
• Citações Web of Science: 17

Resumo

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 naive 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-alpha and IFN-gamma 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 naive 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. (C) 2010 Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 02/07430-6 - Alteracoes de expressao genica na sepse e tolerancia a lps: analise da participacao do oxido nitrico na regulacao genica da sepse.
• Beneficiário: Francisco Garcia Soriano
• Modalidade de apoio: Auxílio à Pesquisa - Regular