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

Scientific paper - Original scientific paper

• Author: Lada Rumora
• Author: Ivona Markelić
• Author: Iva Hlapčić
• Author: Andrea Hulina Tomašković
• Author: Marija Fabijanec
• Author: Feđa Džubur
• Author: Miroslav Samaržija
• Author: Andrea Vukić Dugac
• Author's institution: University of Zagreb; School of Medicine; (Department of Internal Medicine)
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Intensive Care

Abstract (english)

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.

• Keywords (english): Adenosine Triphosphate / blood; Adenosine Triphosphate / metabolism; Aged; Female; HSP70 Heat-Shock Proteins / blood; HSP70 Heat-Shock Proteins / metabolism; Humans; Inflammasomes / metabolism; Interleukin-1beta / blood; Interleukin-1beta / metabolism; Lung Transplantation* / adverse effects; Male; Middle Aged; NLR Family, Pyrin Domain-Containing 3 Protein / metabolism; Pulmonary Disease, Chronic Obstructive / blood; Pulmonary Disease, Chronic Obstructive / diagnosis; Pulmonary Disease, Chronic Obstructive / immunology
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Published version
• Journal title: Immunologic Research
• Numbering: vol. 72, no. 5, pp. 964-974
• p-ISSN: 0257-277X
• e-ISSN: 1559-0755
• DOI: https://doi.org/10.1007/s12026-024-09497-2
• URN:NBN: urn:nbn:hr:105:722126
• Publication: 2024-10
• Project: Number: IP-2014-09-1247; Title (croatian): Uloga stresnog proteina Hsp70 u imunosno-upalnom odgovoru kod kronične opstrukcijske plućne bolesti; Title (english): The role of stress protein Hsp70 in immune and inflammatory responses in chronic obstructive pulmonary disease; Acronym: Hsp70COPD; Jurisdiction: Croatia; Funding stream: Research Projects
• Project: Number: KK.01.1.1.02.0021; Title (croatian): Jačanje znanstveno-istraživačkih i inovacijskih kapaciteta Farmaceutsko-biokemijskog fakulteta Sveučilišta u Zagrebu; Title (english): -; Acronym: FarmInova; Leader: Jasmina Lovrić; Jurisdiction: eu; Funding stream: European Regional Development Fund
• Document URL: https://link.springer.com/10.1007/s12026-024-09497-2
• Type of resource: Text
• Access conditions: Open access
• Created on: 2025-02-03 09:59:54