4.7 Article

Activation of NLRP3 inflammasome in stable chronic obstructive pulmonary disease

Journal

SCIENTIFIC REPORTS
Volume 12, Issue 1, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41598-022-11164-1

Keywords

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Funding

  1. Croatian Science Foundation [IP-2014-091247]
  2. Young researchers career development project-training of doctoral students of the Croatian Science Foundation - European Union from the European Social Fund
  3. project Strengthening the scientific research and innovation capacities of Faculty of Pharmacy and Biochemistry, University of Zagreb [KK.01.1.1.02.0021]
  4. European Regional Development Fund

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The activation of NLRP3 inflammasome, as indicated by increased expression levels of IL1B, NLRP3, CASP1 and elevated IL-1 beta concentration, is observed in patients with stable COPD, suggesting its involvement in the pathogenesis and chronic inflammation of COPD.
Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation plays an important role in chronic obstructive pulmonary disease (COPD) pathogenesis and might be involved in ongoing chronic inflammation. This study aimed to determine interleukin-1beta (IL-1 beta) plasma concentration as well as IL1B, NLRP3 and caspase-1 (CASP1) gene expression in the Croatian COPD patients. 109 patients with stable COPD and age- and sex-matched 95 controls were included in the study. Plasma IL-1 beta concentration was measured by Luminex technology, and gene expression analysis was performed using TaqMan assays. It was shown that COPD patients had increased concentration of IL-1 beta and enhanced gene expression of IL1B, NLRP3 and CASP1 compared to controls. There was no difference in IL-1 beta or IL1B, NLRP3 and CASP1 in patients with COPD regarding airflow obstruction severity and smoking history. Finally, the diagnostic potential of the determined parameters was evaluated, and it was found that IL-1 beta correctly classified 89% of cases in the combination with common inflammatory biomarkers, white blood cell count and fibrinogen, showing a potential in COPD prediction. In conclusion, up-regulation of IL1B, NLRP3, CASP1 and increased IL-1 beta concentration suggest the activation of NLRP3 inflammasome in the systemic compartment of patients with stable COPD.

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