Assessment of NLRP3 inflammasome activation in patients with chronic obstructive pulmonary disease before and after lung transplantation

• Published in: Immunologic research 2024-10, Vol.72 (5), p.964-974
• Main Authors: Rumora, Lada, Markelić, Ivona, Hlapčić, Iva, Tomašković, Andrea Hulina, Fabijanec, Marija, Džubur, Feđa, Samaržija, Miroslav, Dugac, Andrea Vukić
• Format: Article
• Language: English
• Subjects: Adenosine receptors; Adenosine triphosphate; Adenosine Triphosphate - blood; Adenosine Triphosphate - metabolism; Aged; Allergology; Biomedical and Life Sciences; Biomedicine; Carbon monoxide; Chronic obstructive pulmonary disease; Enzyme-linked immunosorbent assay; Female; Gene expression; Graft rejection; Heat shock proteins; HSP70 Heat-Shock Proteins - blood; HSP70 Heat-Shock Proteins - metabolism; Hsp70 protein; Humans; IL-1β; Immunology; Inflammasomes; Inflammasomes - metabolism; Interleukin-1beta - blood; Interleukin-1beta - metabolism; Internal Medicine; Lung diseases; Lung transplantation; Lung Transplantation - adverse effects; Lung transplants; Male; Medicine/Public Health; Middle Aged; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Pattern recognition receptors; Peripheral blood; Population levels; Pulmonary Disease, Chronic Obstructive - blood; Pulmonary Disease, Chronic Obstructive - diagnosis; Pulmonary Disease, Chronic Obstructive - immunology; Purine receptors; Pyrin protein; Receptor mechanisms; Respiratory function; TLR2 protein; TLR4 protein; Toll-like receptors
• ISSN: 0257-277X; 1559-0755; 1559-0755
• DOI: 10.1007/s12026-024-09497-2

The interplay between purinergic receptors as well as pattern recognition receptors like Toll-like receptors (TLRs) and NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) might have a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of this study was to determine and compare the concentrations of the damage-associated molecular patterns (DAMPs) heat shock protein 70 (Hsp70) and adenosine triphosphate (ATP), and gene expression of their respective receptors as well as NLRP3 inflammasome-related molecules in the peripheral blood of patients with end-stage COPD before and 1 year after lung transplantation (LT). Lung function was assessed by spirometry and diffusion capacity for carbon monoxide (DLCO). Quantitative polymerase chain reaction (qPCR) was applied for detection of TLR2 , TLR4 , P2X7R , P2Y2R , IL1B , CASP1 , and NLRP3 expression. High-sensitivity ELISA kits were used for extracellular (e) Hsp70 and IL-1β, and luminescence assay for eATP measurements. Concentrations of eHsp70 and eATP as well as IL-1β were significantly increased in the plasma of end-stage COPD patients and significantly decreased after LT. In addition, TLR4 , P2Y2R , IL1B , CASP1 , and NLRP3 expression was up-regulated in COPD patients before LT, while it was significantly suppressed after LT. In conclusion, it could be assumed that NLRP3 inflammasome is activated in the peripheral blood of end-stage COPD patients and that eHsp70 and eATP could be responsible for its activation through triggering their receptors. On the other hand, previously enhanced pro-inflammatory reactions seem to be suppressed to the healthy population levels in lung recipients without allograft rejection.