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)‐1β gene expression as well as IL‐1β 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.

中文翻译：

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COPD急性加重的单核细胞和支气管上皮细胞模型中NLRP3炎症小体激活的病原体相关分子模式和细胞外Hsp70相互作用

在慢性阻塞性肺疾病 (COPD) 恶化期间，病原体相关分子模式 (PAMP；例如脂多糖 (LPS) 和脂磷壁酸 (LTA)) 和损伤相关分子模式 (DAMP；例如细胞外热休克蛋白 70 (eHsp70) 之间的相互作用和三磷酸腺苷 (ATP)) 可能会影响患者的预后。核苷酸结合寡聚化结构域样受体家族含 pyrin 结构域 3 (NLRP3) 炎症小体可能在 COPD 免疫系统功能障碍中起作用。我们假设 LPS、LTA、eHsp70 及其组合诱导 NLRP3 炎症小体激活，我们旨在探索这一假设。我们使用单核细胞（单核细胞衍生的巨噬细胞 (MDMs) 和 THP-1）和支气管上皮细胞（NHBE 和 NCI-H292）来代表可能在 COPD 中受到影响的全身和局部气道隔室。与未处理的细胞相比，细菌成分和 eHsp70 刺激了所有细胞的 NLRP3 和白细胞介素 (IL)-1β 基因表达以及 IL-1β 和 ATP 的释放。LDH 分泌仅在细胞系中被诱导。与单独的 PAMP 相比，eHsp70 对 eATP 水平具有抑制 (NCI-H292) 或刺激 (NHBE) 作用。关于 NLRP3 炎症小体激活，eHsp70 主要具有拮抗作用。我们证明细菌成分和 eHsp70 激活 NLRP3 炎性体并增加 ATP 分泌。