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

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 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.