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

• Published in: Immunologic research Vol. 72; no. 5; pp. 964 - 974
• Main Authors: Rumora, Lada, Markelić, Ivona, Hlapčić, Iva, Tomašković, Andrea Hulina, Fabijanec, Marija, Džubur, Feđa, Samaržija, Miroslav, Dugac, Andrea Vukić
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-10-2024; Springer Nature B.V
• Subjects: Adenosine receptors; Allergology; ATP; Biomedical and Life Sciences; Biomedicine; Carbon monoxide; Chronic obstructive pulmonary disease; Enzyme-linked immunosorbent assay; Gene expression; Graft rejection; Heat shock proteins; Hsp70 protein; IL-1β; Immunology; Inflammasomes; Internal Medicine; Lung diseases; Lung transplantation; Lung transplants; Medicine/Public Health; Pattern recognition receptors; Peripheral blood; Population levels; Purine receptors; Pyrin protein; Receptor mechanisms; Respiratory function; TLR2 protein; TLR4 protein; Toll-like receptors; NLRP3; Hsp70; ATP; Lung transplantation; COPD
• 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.