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

Int J Mol Med. 2018 Feb;41(2):757-764. doi: 10.3892/ijmm.2017.3310. Epub 2017 Dec 5.

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.

MeSH terms

  • Allergens / administration & dosage
  • Allergens / immunology
  • Antigens, Dermatophagoides / administration & dosage
  • Antigens, Dermatophagoides / immunology*
  • Arthropod Proteins / administration & dosage
  • Arthropod Proteins / immunology*
  • Bronchi / cytology
  • Bronchi / immunology
  • Bronchi / pathology
  • Caspase 1 / genetics
  • Caspase Inhibitors / administration & dosage
  • Cell Death / genetics
  • Cells, Cultured
  • Cysteine Endopeptidases / administration & dosage
  • Cysteine Endopeptidases / immunology*
  • Epithelial Cells / metabolism
  • Gene Knockdown Techniques
  • Humans
  • Inflammasomes / genetics
  • Inflammasomes / metabolism
  • Inflammation / genetics*
  • Inflammation / immunology
  • Inflammation / pathology
  • Interleukin-1beta / genetics*
  • Interleukin-1beta / metabolism
  • L-Lactate Dehydrogenase / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / antagonists & inhibitors
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics*
  • Pyroptosis / genetics*

Substances

  • Allergens
  • Antigens, Dermatophagoides
  • Arthropod Proteins
  • Caspase Inhibitors
  • Inflammasomes
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • L-Lactate Dehydrogenase
  • Cysteine Endopeptidases
  • Dermatophagoides farinae antigen f 1
  • Caspase 1