Inflammasome gene profile is modulated in septic patients, with a greater magnitude in non-survivors

Inflammasome gene profile is modulated in septic patients, with a greater magnitude in non-survivors

Author Esquerdo, K. F. Autor UNIFESP Google Scholar
Sharma, N. K. Autor UNIFESP Google Scholar
Brunialti, M. K. C. Autor UNIFESP Google Scholar
Baggio-Zappia, G. L. Autor UNIFESP Google Scholar
Assuncao, M. Google Scholar
Azevedo, L. C. P. Google Scholar
Bafi, A. T. Autor UNIFESP Google Scholar
Salomao, R. Autor UNIFESP Google Scholar
Abstract Inflammasome signalling induces the processing and secretion of interleukin (IL)-1 and IL-18 which, coupled with pyroptosis, activate further the inflammatory response. In the present study we evaluated the expression of genes involved in inflammasome signalling pathways in septic patients, their interaction networks and the predicted functions modulated in survivors and non-survivors. Twenty-seven patients with sepsis secondary to community-acquired pneumonia admitted to intensive care units from three general hospitals in SAo Paulo were included into the study. We performed a polymerase chain reaction (PCR) array encompassing 35 genes related to the nucleotide-binding oligomerization domain and leucine-rich repeat-containing (NLR)-inflammasome in peripheral blood mononuclear cells obtained at admission and after 7 days of follow-up. Eleven healthy volunteers were used as the reference group. Increased NLRC4 and NLRP3 and decreased nucleotide-binding oligomerization domain (NOD1), and NLRP1 expression was observed in septic patients compared to healthy individuals

the IL-1 and IL-18 expression levels were also high in the patients. The gene expression changes followed the same patterns in surviving and non-surviving patients, with higher magnitudes observed in non-survivors. Functional analyses revealed, however, that activation and inhibition intensity for representing functions were different in survivors and non-survivors, as for production of reactive oxygen species, synthesis of nitric oxide and for the control of bacterial infections. Our results showed that the genes involved in the activation of the NLR-inflammasome cascades were altered substantially in septic patients, with a higher number of altered genes and a higher intensity in the disturbance of gene expression found among patients dying of sepsis.
Keywords interleukin-18
Toll-like receptor
Language English
Sponsor Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
Grant number FAPESP: 2011/20401-4
CNPq: 305685/2011-2
Date 2017
Published in Clinical And Experimental Immunology. Hoboken, v. 189, n. 2, p. 232-240, 2017.
ISSN 0009-9104 (Sherpa/Romeo, impact factor)
Publisher Wiley
Extent 232-240
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000405634300011

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