Esquerdo K F, Sharma N K, Brunialti M K C, Baggio-Zappia G L, Assunção M, Azevedo L C P, Bafi A T, Salomao R
Escola Paulista de Medicina, Hospital São Paulo, Universidade Federal de Sao Paulo, São Paulo, Brazil.
Hospital Israelita Albert Einstein, São Paulo, Brazil.
Clin Exp Immunol. 2017 Aug;189(2):232-240. doi: 10.1111/cei.12971. Epub 2017 Apr 20.
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.
炎性小体信号传导诱导白细胞介素（IL）-1β和IL-18的加工与分泌，这二者与细胞焦亡一起进一步激活炎症反应。在本研究中，我们评估了脓毒症患者中炎性小体信号通路相关基因的表达、它们的相互作用网络以及在幸存者和非幸存者中调节的预测功能。纳入了来自圣保罗三家综合医院重症监护病房的27例社区获得性肺炎继发脓毒症患者。我们对入院时及随访7天后获得的外周血单核细胞中与核苷酸结合寡聚化结构域和富含亮氨酸重复序列（NLR）-炎性小体相关的35个基因进行了聚合酶链反应（PCR）阵列分析。11名健康志愿者作为参照组。与健康个体相比，脓毒症患者中观察到NLRC4和NLRP3增加，核苷酸结合寡聚化结构域（NOD1）和NLRP1表达降低；患者中IL-1β和IL-18表达水平也较高。存活和非存活患者的基因表达变化遵循相同模式，非存活患者中变化幅度更大。然而，功能分析显示，在幸存者和非幸存者中，代表功能的激活和抑制强度不同，如活性氧的产生、一氧化氮的合成以及细菌感染的控制。我们的结果表明，参与NLR-炎性小体级联激活的基因在脓毒症患者中发生了显著改变，在死于脓毒症的患者中发现更多的基因改变和更高强度的基因表达紊乱。
