Der f1 induces pyroptosis in human bronchial epithelia via the NLRP3 inflammasome

Abstract

Damage to the bronchial epithelium leads to persistent inflammation and airway remodelling in various respiratory diseases, such as asthma and chronic obstructive pulmonary disease. To date, the mechanisms underlying bronchial epithelial cell damage and death by common allergens remain largely unknown. The aim of the present study was to investigate Der f1, an allergen of Dermatophagoides farinae, which may result in the death of human bronchial epithelial cells (HBECs). Der f1 induces BECs to undergo the inflammatory cell death referred to as pyroptosis, induced by increasing lactate dehydrogenase release and propidium iodide penetration. Stimulation by Der f1 enhances interleukin (IL)-1β cleavage and release, which is associated with caspase-1 activation. In addition, the NOD-like receptor family pyrin domain-containing 3 (NLRP3), is required for the activation of caspase-1 through increasing the formation of the inflammasome complex. Consistent with these findings, pre-treatment of HBECs with a caspase-1 inhibitor, or silencing of NLRP3 by siRNA transfection, reduced Der f1-mediated IL-1β and pyroptosis. Therefore, the common allergen Der f1 was not only found to induce allergy, but also led to pyroptosis and IL-1β secretion via the NLRP3-caspase-1 inflammasome in HBECs. This newly identified connection of the Der f1 allergen with BEC damage and inflammation may play an important role in the pathogenesis of asthma.

Caspase-11 promotes allergic airway inflammation

“…While cell death in asthma has been quite intensively studied, researchers focused predominantly on the role of apoptosis 52 . It has been recently shown that common allergens can drive pyroptosis and contribute to asthma 53 . Taken with the effect of NSAIDs presented here, and previous data demonstrating a beneficial effect for a global caspase inhibitor 54 , limiting pyroptosis becomes even more relevant as a therapeutic strategy for asthma and possibly other respiratory diseases, such as COPD.…”

Ageratina adenophora induces mice hepatotoxicity via ROS-NLRP3-mediated pyroptosis

“…Previous studies have demonstrated that pyroptosis is emerging as a ubiquitous immune effector in a variety of cells 18 , 21 . It can be triggered by various infections and non-infections stimulates 22 . In the process, cells recognize foreigner signals and secrete pro-inflammatory cytokines as well as release intracellular contents 23 .…”

Update of inflammasome activation in microglia/macrophage in aging and aging‐related disease

“…Inflammasome activation was first discovered in myeloid cells, including macrophage/microglia, neutrophil, and dendritic cell . Recently, it was demonstrated that other cell types, including, oligodendrocyte, astrocyte, neurons, and epithelial cell, could also trigger inflammasome activation . Among inflammasome‐forming cells, it is microglia/macrophage that has the most potent inflammasome activation, thus is most widely studied …”

“…7 Recently, it was demonstrated that other cell types, including, oligodendrocyte, astrocyte, neurons, and epithelial cell, could also trigger inflammasome activation. [8][9][10][11] Among inflammasome-forming cells, it is microglia/macrophage that has the most potent inflammasome activation, thus is most widely studied. 12 Classically, inflammasome is composed of sensor, executor, and substrate.…”