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Cigarette smoke and extracellular Hsp70 induce secretion of ATP and differential activation of NLRP3 inflammasome in monocytic and bronchial epithelial cells

Background: Chronic obstructive pulmonary disease (COPD) is an inflammatory disease mainly caused by smoking. Cigarette smoke damages airway epithelium and activates lung macrophages, causing inflammatory responses. It was suggested that nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome might have an important role in COPD development. Study aimed to explore whether cigarette smoke extract (CSE), extracellular heat shock protein 70 (eHsp70) or their combinations induce adenosine triphosphate (ATP) release and NLRP3 inflammasome activation. Methods: We detected NLRP3 and interleukin (IL)-1β mRNA expression, extracellular IL-1β and ATP concentrations as well as lactate dehydrogenase (LDH) activity. We used bronchial epithelial (NCI-H292, 16HBE and NHBE) and monocytic cells (monocyte-derived macrophages (MDMs) and THP-1) as representative of local airway and systemic compartments that could be affected in COPD. Results: CSE and eHsp70 increased NLRP3 and IL-1β mRNA expression as well as IL-1β and ATP secretion in all cells compared to untreated cells. Lytic cell death was observed in cell lines, especially those of bronchial epithelium origin, but not in primary cells (NHBE, MDMs). Regarding LDH activity, eHsp70 did not modulate CSE effects, except in NCI-H292 cell line. However, eHsp70 significantly affected CSE-provoked NLRP3 inflammasome activation by causing mostly antagonistic effects in airway epithelial cells and synergistic effects in MDMs. Conclusion: We demonstrated that both CSE and eHsp70 induce ATP secretion and differential activation of NLRP3 inflammasome in bronchial epithelial and monocytic cells. We suggest that these mechanisms might be involved in pathophysiology of COPD by contributing to the propagation of inflammation.

COPD ; cigarette smoke ; extracellular Hsp70 ; NLRP3 inflammasome ; ATP

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