Journal
APMIS
Volume 129, Issue 2, Pages 80-90Publisher
WILEY
DOI: 10.1111/apm.13089
Keywords
COPD exacerbations; lipopolysaccharide; lipoteichoic acid; extracellular Hsp70; NLRP3 inflammasome; adenosine triphosphate
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Funding
- Croatian Science Foundation [IP-2014-09-1247]
- Croatian Science Foundation - European Union from the European Social Fund
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This study suggests that bacterial components and extracellular heat shock protein 70 (eHsp70) can activate the NLRP3 inflammasome and increase ATP secretion, potentially modulating immune responses during bacterial infections and impacting outcomes in COPD patients during acute exacerbations.
During chronic obstructive pulmonary disease (COPD) exacerbations, interplay between pathogen-associated molecular patterns (PAMPs; e.g. lipopolysaccharide (LPS) and lipoteichoic acid (LTA)) and damage-associated molecular patterns (DAMPs; e.g. extracellular heat shock protein 70 (eHsp70) and adenosine triphosphate (ATP)) might influence patient's outcome. Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome might have a role in dysfunctional immune system in COPD. We hypothesized that LPS, LTA, eHsp70 and their combinations induce NLRP3 inflammasome activation, and we aimed to explore this assumption. We used monocytic (monocyte-derived macrophages (MDMs) and THP-1) and bronchial epithelial cells (NHBE and NCI-H292) to represent systemic and local airway compartments that could be affected in COPD. Bacterial components and eHsp70 stimulated NLRP3 and interleukin (IL)-1 beta gene expression as well as IL-1 beta and ATP release from all cells compared to non-treated cells. LDH secretion was induced in cell lines only. eHsp70 had inhibitory (NCI-H292) or stimulatory (NHBE) effects on eATP levels compared to PAMP alone. Regarding NLRP3 inflammasome activation, eHsp70 had mostly antagonistic effects. We demonstrated that bacterial components and eHsp70 activate NLRP3 inflammasome and increase ATP secretion. We suggest that extracellular Hsp70 might modulate immune responses provoked by bacterial infections and affect COPD patients' outcome during acute exacerbations.
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