title: Inflammasome gene profile is modulated in septic patients, with a greater magnitude in non-survivors.
abstract: Inflammasome signalling induces the processing and secretion of interleukin (IL)-1β 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 São 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-1β 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.
authors.affiliation: Escola Paulista de Medicina, Hospital São Paulo, Universidade Federal de Sao Paulo, São Paulo, Brazil.
authors.forename: K F
authors.initials: KF
authors.lastname: Esquerdo
authors.affiliation: Escola Paulista de Medicina, Hospital São Paulo, Universidade Federal de Sao Paulo, São Paulo, Brazil.
authors.forename: N K
authors.initials: NK
authors.lastname: Sharma
authors.affiliation: Escola Paulista de Medicina, Hospital São Paulo, Universidade Federal de Sao Paulo, São Paulo, Brazil.
authors.forename: M K C
authors.initials: MKC
authors.lastname: Brunialti
authors.affiliation: Escola Paulista de Medicina, Hospital São Paulo, Universidade Federal de Sao Paulo, São Paulo, Brazil.
authors.forename: G L
authors.initials: GL
authors.lastname: Baggio-Zappia
authors.affiliation: Hospital Israelita Albert Einstein, São Paulo, Brazil.
authors.forename: M
authors.initials: M
authors.lastname: Assunção
authors.affiliation: Hospital Sírio-Libanes, São Paulo, Brazil.
authors.forename: L C P
authors.initials: LCP
authors.lastname: Azevedo
authors.affiliation: Escola Paulista de Medicina, Hospital São Paulo, Universidade Federal de Sao Paulo, São Paulo, Brazil.
authors.forename: A T
authors.initials: AT
authors.lastname: Bafi
authors.affiliation: Escola Paulista de Medicina, Hospital São Paulo, Universidade Federal de Sao Paulo, São Paulo, Brazil.
authors.forename: R
authors.identifier: 0000-0003-1149-4598
authors.initials: R
authors.lastname: Salomao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001938:Brazil; D016022:Case-Control Studies; D002460:Cell Line; D017714:Community-Acquired Infections / Q000150:complications*; D005260:Female; D015870:Gene Expression; D006801:Humans; D058847:Inflammasomes / Q000235:genetics*; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics / Q000378:metabolism; D011446:Prospective Studies; D000069292:Pyroptosis; D017382:Reactive Oxygen Species / Q000378:metabolism; D018805:Sepsis / Q000235:genetics*; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D017382:Reactive Oxygen Species; D051193:Toll-Like Receptors
keywords: NLRP3; Toll-like receptor; interleukin-18; interleukin-1beta; pyroptosis