Toll interacting protein protects bronchial epithelial cells from bleomycin-induced apoptosis.
Antibiotics, Antineoplastic
/ adverse effects
Apoptosis
Autophagy
Bleomycin
/ adverse effects
Bronchi
/ cytology
Epithelial Cells
/ cytology
Humans
Idiopathic Pulmonary Fibrosis
/ chemically induced
Intracellular Signaling Peptides and Proteins
/ genetics
Mitochondria
/ drug effects
Protective Agents
Reactive Oxygen Species
/ metabolism
TOLLIP
apoptosis
autophagy
basal cells
idiopathic pulmonary fibrosis
lung epithelial cells
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
28
10
2019
revised:
10
04
2020
accepted:
20
04
2020
pubmed:
1
7
2020
medline:
2
3
2021
entrez:
30
6
2020
Statut:
ppublish
Résumé
Idiopathic pulmonary fibrosis (IPF) is characterized by altered epithelial cell phenotypes, which are associated with myofibroblast accumulation in the lung. Atypical alveolar epithelial cells in IPF express molecular markers of airway epithelium. Polymorphisms within and around Toll interacting protein (TOLLIP) are associated with the susceptibility to IPF and mortality. However, the functional role of TOLLIP in IPF is unknown. Using lung tissues from IPF and control subjects, we showed that expression of TOLLIP gene in the lung parenchyma is globally lower in IPF compared to controls. Lung cells expressing significant levels of TOLLIP include macrophages, alveolar type II, and basal cells. TOLLIP protein expression is lower in the parenchyma of IPF lungs but is expressed in the atypical epithelial cells of the distal fibrotic regions. Using overexpression and silencing approaches, we demonstrate that TOLLIP protects cells from bleomycin-induced apoptosis using primary bronchial epithelial cells and BEAS-2B cells. The protective effects are mediated by reducing mitochondrial reactive oxygen species (ROS) levels and upregulating autophagy. Therefore, global downregulation of the TOLLIP gene in IPF lungs may predispose injured lung epithelial cells to apoptosis and to the development of IPF.
Identifiants
pubmed: 32596871
doi: 10.1096/fj.201902636RR
pmc: PMC8175118
mid: NIHMS1708163
doi:
Substances chimiques
Antibiotics, Antineoplastic
0
Intracellular Signaling Peptides and Proteins
0
Protective Agents
0
Reactive Oxygen Species
0
TOLLIP protein, human
0
Bleomycin
11056-06-7
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
9884-9898Subventions
Organisme : NIAID NIH HHS
ID : R01 AI133351
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL135062
Pays : United States
Organisme : NIAMS NIH HHS
ID : R21 AR076024
Pays : United States
Informations de copyright
© 2020 Federation of American Societies for Experimental Biology.
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