Gene expression reprogramming protects macrophage from septic-induced cell death


Autoria(s): MELO, Edielle Sant`Anna; BARBEIRO, Denise F.; GORJAO, Renata; RIOS, Ester Correia Sarmento; VASCONCELOS, Dewton; VELASCO, Irineu T.; SZABO, Csaba; CURI, Rui; LIMA-SALGADO, Thais Martins de; SORIANO, Francisco Garcia
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

19/10/2012

19/10/2012

2010

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.

FAPESP[02/07430-6]

CNPq[470744/2004-9]

Identificador

MOLECULAR IMMUNOLOGY, v.47, n.16, p.2587-2593, 2010

0161-5890

http://producao.usp.br/handle/BDPI/21704

10.1016/j.molimm.2010.06.011

http://dx.doi.org/10.1016/j.molimm.2010.06.011

Idioma(s)

eng

Publicador

PERGAMON-ELSEVIER SCIENCE LTD

Relação

Molecular Immunology

Direitos

restrictedAccess

Copyright PERGAMON-ELSEVIER SCIENCE LTD

Palavras-Chave #Sepsis #Macrophage #Apoptosis #Immunoparalysia #Necrosis #Gene expression #POLY(ADP-RIBOSE) POLYMERASE-1 #NEUTROPHIL MIGRATION #NITROSATIVE STRESS #INNATE IMMUNITY #GERMINAL CENTER #SEVERE SEPSIS #NITRIC-OXIDE #CD40 LIGAND #IRAK-M #INFLAMMATION #Biochemistry & Molecular Biology #Immunology
Tipo

article

original article

publishedVersion