Resveratrol attenuates inflammation and apoptosis through alleviating endoplasmic reticulum stress via Akt/mTOR pathway in fungus-induced allergic airways inflammation.
Int Immunopharmacol
; 103: 108489, 2022 Feb.
Article
in En
| MEDLINE
| ID: mdl-34968999
ABSTRACT
BACKGROUND:
Resveratrol has shown pleiotropic effects against inflammation and oxidative response. The present study aimed to investigate the effects and mechanisms of resveratrol on fungus-induced allergic airway inflammation.METHODS:
Female BALB/c mice were injected intraperitoneally with Aspergillus fumigatus (Af) extract emulsified with aluminum on day 0 and 7 and intranasally challenged with Af extracts on day 14 and 15. Resveratrol or dexamethasone or a vehicle was injected intraperitoneally 1 h before each challenge. Mice were sacrificed for serum, bronchoalveolar lavage fluid (BALF), and lungs 24 h after the last challenge. The control group was administered with saline. BEAS-2B was used for the experiments in vitro that Af-exposed airway epithelial cells.RESULTS:
Resveratrol and dexamethasone attenuated the airway inflammation and eosinophilia, and reduced not only the production of IL-4, IL-5, and IL-13 in the BALF and lung tissues but also the mRNA levels of lung IL-6, TNF-α, and TGF-ß induced by Af challenge (P < 0.05). Furthermore, Af-induced lung endoplasmic reticulum (ER) stress-related proteins PERK, CHOP, and GRP78 and the apoptosis markers including cleaved caspase-3 and cleaved caspase-7 were both suppressed significantly by resveratrol (P < 0.05). In vitro, activation of ER stress and the Akt/mTOR pathway in Af-exposed BEAS-2B cells were effectively ameliorated by resveratrol. Inhibition of the Akt/mTOR pathway using LY294002 suppressed the ER stress while ER stress inhibitor 4-PBA decreased the apoptosis in Af-exposed BEAS-2B cells.CONCLUSIONS:
Our findings collectively revealed that resveratrol alleviated the Af-exposed allergic inflammation and apoptosis through inhibiting ER stress via Akt/mTOR pathway, exerting therapeutic effects on the fungus-induced allergic lung disorder.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Proto-Oncogene Proteins c-akt
/
Endoplasmic Reticulum Stress
Limits:
Animals
Language:
En
Journal:
Int Immunopharmacol
Journal subject:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Year:
2022
Document type:
Article
Affiliation country:
China