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

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Title: Assessment of NLRP3 inflammasome activation in patients with chronic obstructive pulmonary disease before and after lung transplantation
Authors: Rumora, Lada, Markelić, Ivona, Hlapčić, Iva, Hulina Tomašković, Andrea, Fabijanec, Marija, Džubur, Feđa, Samaržija, Miroslav, Vukić Dugac, Andrea
Source: Immunol Res
Publisher Information: Research Square Platform LLC, 2023.
Publication Year: 2023
Subject Terms: Male, 0301 basic medicine, HSP70 Heat-Shock Proteins / metabolism, Adenosine Triphosphate / metabolism, Inflammasomes, Interleukin-1beta, Interleukin-1beta / metabolism, NLR Family, Pyrin Domain-Containing 3 Protein / metabolism, Hsp70, Pulmonary Disease, Chronic Obstructive, 03 medical and health sciences, Adenosine Triphosphate, HSP70 Heat-Shock Proteins / blood, NLRP3, Pulmonary Disease, Chronic Obstructive / blood, NLR Family, Pyrin Domain-Containing 3 Protein, lung transplantation, COPD, Humans, Pulmonary Disease, Chronic Obstructive / immunology, HSP70 Heat-Shock Proteins, Lung Transplantation* / adverse effects, Aged, 0303 health sciences, Adenosine Triphosphate / blood, Research, Middle Aged, 3. Good health, ATP, Interleukin-1beta / blood, Pulmonary Disease, Chronic Obstructive / diagnosis, Female, Inflammasomes / metabolism, Lung Transplantation
Description: 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 one 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 eHsp70 and IL-1β, and luminescence assay for eATP measurements. Concentrations of eHsp70 and eATP as well as IL-1β were significantly increased in 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 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.
Document Type: Article
Other literature type
File Description: application/pdf
ISSN: 1559-0755
0257-277X
DOI: 10.21203/rs.3.rs-3667084/v1
DOI: 10.1007/s12026-024-09497-2
Access URL: https://pubmed.ncbi.nlm.nih.gov/38811459
Rights: CC BY
Accession Number: edsair.doi.dedup.....6d7383d07944211299cd5ddc37ee50db
Database: OpenAIRE
Description
Abstract: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 one 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 eHsp70 and IL-1β, and luminescence assay for eATP measurements. Concentrations of eHsp70 and eATP as well as IL-1β were significantly increased in 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 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.
ISSN:15590755
0257277X
DOI:10.21203/rs.3.rs-3667084/v1