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Toluene diisocyanate-induced inflammation and airway remodeling involves autophagy in human bronchial epithelial cells.

Abstract
Toluene-diisocyanate (TDI) is one of the main causes of occupational asthma. To study the role of autophagy in TDI-induced airway inflammation and airway remodeling in bronchial airway epithelial (16HBE) cells. We treated 16HBE cells with TDI-human serum albumin (TDI-HSA) conjugate to observe reactive oxygen species (ROS) release, autophagy activation, airway inflammation and airway remodeling. 3-Methyladenine (3-MA) and Rapamycin (Rapa) intervention were used to explore the effects of autophagy on inflammatory response and protein expression related to airway remodeling in 16HBE cells treated with TDI-HSA. Experimental results suggested that various concentrations of TDI-HSA (0, 40, 80 and 120 μg/mL) increased the release of ROS and the expression of Nrf2, activated autophagy and increased the expression of AMPK, Beclin-1, LC3 and decreased the expression of p62, promoted the levels of IL-5, IL-6 and IL-8 in 16HBE cells. Results also showed that E-cadherin expression decreased but an increase was observed in α-SMA and MMP-9 in the TDI-HSA group. The treatment of TDI-HSA combined with Rapa aggravated the above reaction whereas the inverse was true for TDI-HSA combined with 3-MA. These results indicated that autophagy is involved in TDI-induced airway inflammation and airway remodeling as a positive regulatory mechanism, inhibiting autophagy can significantly alleviate the TDI-induced inflammatory response and attenuate airway remodeling protein expression in 16HBE cells.
AuthorsBo Jiao, Yujun Chen, Yuting Yang, Linlin Sai, Gongchang Yu, Cunxiang Bo, Yu Zhang, Cheng Peng, Qiang Jia, Hua Shao
JournalToxicology in vitro : an international journal published in association with BIBRA (Toxicol In Vitro) Vol. 70 Pg. 105040 (Feb 2021) ISSN: 1879-3177 [Electronic] England
PMID33127434 (Publication Type: Journal Article)
CopyrightCopyright © 2020 Elsevier Ltd. All rights reserved.
Chemical References
  • Allergens
  • Cytokines
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Reactive Oxygen Species
  • Toluene 2,4-Diisocyanate
  • Serum Albumin, Human
Topics
  • Airway Remodeling (drug effects)
  • Allergens (toxicity)
  • Autophagy (drug effects)
  • Bronchi (cytology)
  • Cell Line
  • Cell Survival (drug effects)
  • Cytokines (metabolism)
  • Epithelial Cells (drug effects, metabolism)
  • Humans
  • Inflammation (chemically induced, metabolism)
  • NF-E2-Related Factor 2 (metabolism)
  • Reactive Oxygen Species (metabolism)
  • Serum Albumin, Human (toxicity)
  • Toluene 2,4-Diisocyanate (toxicity)

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