TNFα selectively activates the IRE1α/XBP1 endoplasmic reticulum stress pathway in human airway smooth muscle cells.
Cells, Cultured
Endoplasmic Reticulum
/ drug effects
Endoplasmic Reticulum Stress
/ drug effects
Endoribonucleases
/ genetics
Eukaryotic Initiation Factor-2
/ genetics
Humans
Muscle, Smooth, Vascular
/ drug effects
Phosphorylation
Protein Serine-Threonine Kinases
/ genetics
Signal Transduction
Tumor Necrosis Factor-alpha
/ pharmacology
Unfolded Protein Response
/ drug effects
X-Box Binding Protein 1
/ genetics
eIF-2 Kinase
/ genetics
ER stress
TNFα
airway smooth muscle
asthma
inflammation
Journal
American journal of physiology. Lung cellular and molecular physiology
ISSN: 1522-1504
Titre abrégé: Am J Physiol Lung Cell Mol Physiol
Pays: United States
ID NLM: 100901229
Informations de publication
Date de publication:
01 03 2020
01 03 2020
Historique:
pubmed:
16
1
2020
medline:
22
7
2020
entrez:
16
1
2020
Statut:
ppublish
Résumé
Airway inflammation is a key aspect of diseases such as asthma. Proinflammatory cytokines such as TNFα mediate the inflammatory response. In various diseases, inflammation leads to endoplasmic reticulum (ER) stress, the accumulation of unfolded proteins, which triggers homeostatic responses to restore normal cellular function. We hypothesized that TNFα triggers ER stress through an increase in reactive oxygen species generation in human airway smooth muscle (hASM) with a downstream effect on mitofusin 2 (Mfn2). In hASM cells isolated from lung specimens incidental to patient surgery, dose- and time-dependent effects of TNFα exposure were assessed. Exposure of hASM to tunicamycin was used as a positive control. Tempol (500 μM) was used as superoxide scavenger. Activation of three ER stress pathways were evaluated by Western blotting:
Identifiants
pubmed: 31940218
doi: 10.1152/ajplung.00212.2019
pmc: PMC7099431
doi:
Substances chimiques
Eukaryotic Initiation Factor-2
0
TNF protein, human
0
Tumor Necrosis Factor-alpha
0
X-Box Binding Protein 1
0
XBP1 protein, human
0
EIF2AK3 protein, human
EC 2.7.11.1
ERN1 protein, human
EC 2.7.11.1
Protein Serine-Threonine Kinases
EC 2.7.11.1
eIF-2 Kinase
EC 2.7.11.1
Endoribonucleases
EC 3.1.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
L483-L493Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL126451
Pays : United States
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