Chemical Chaperone 4-PBA Mitigates Tumor Necrosis Factor Alpha-Induced Endoplasmic Reticulum Stress in Human Airway Smooth Muscle.
4-phenylbutyric acid
airway smooth muscle
chemical chaperone
endoplasmic reticulum stress
unfolded protein
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
31 Oct 2023
31 Oct 2023
Historique:
received:
02
10
2023
revised:
27
10
2023
accepted:
28
10
2023
medline:
15
11
2023
pubmed:
14
11
2023
entrez:
14
11
2023
Statut:
epublish
Résumé
Airway inflammation and pro-inflammatory cytokines such as tumor necrosis factor alpha (TNFα) underlie the pathophysiology of respiratory diseases, including asthma. Previously, we showed that TNFα activates the inositol-requiring enzyme 1α (IRE1α)/X-box binding protein 1 spliced (XBP1s) endoplasmic reticulum (ER) stress pathway in human airway smooth muscle (hASM) cells. The ER stress pathway is activated by the accumulation of unfolded proteins in the ER. Accordingly, chemical chaperones such as 4-phenylbutyric acid (4-PBA) may reduce ER stress activation. In the present study, we hypothesized that chemical chaperone 4-PBA mitigates TNFα-induced ER stress in hASM cells. hASM cells were isolated from bronchiolar tissue obtained from five patients with no history of smoking or respiratory diseases. The hASM cells' phenotype was confirmed via the expression of alpha-smooth muscle actin and elongated morphology. hASM cells from the same patient sample were then separated into three 12 h treatment groups: (1) TNFα (20 ng/mL), (2) TNFα + 4-PBA (1 μM, 30 min pretreatment), and (3) untreated control. The expressions of total IRE1α and phosphorylated IRE1α (pIRE1α
Identifiants
pubmed: 37958799
pii: ijms242115816
doi: 10.3390/ijms242115816
pmc: PMC10649207
pii:
doi:
Substances chimiques
Tumor Necrosis Factor-alpha
0
4-phenylbutylamine
0
4-phenylbutyric acid
7WY7YBI87E
Endoribonucleases
EC 3.1.-
Protein Serine-Threonine Kinases
EC 2.7.11.1
Phenylbutyrates
0
Molecular Chaperones
0
RNA, Messenger
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL157984
Pays : United States
Organisme : NIH HHS
ID : HL157984
Pays : United States
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