1. Academic Validation
  2. Resveratrol attenuates inflammation and apoptosis through alleviating endoplasmic reticulum stress via Akt/mTOR pathway in fungus-induced allergic airways inflammation

Resveratrol attenuates inflammation and apoptosis through alleviating endoplasmic reticulum stress via Akt/mTOR pathway in fungus-induced allergic airways inflammation

  • Int Immunopharmacol. 2022 Feb;103:108489. doi: 10.1016/j.intimp.2021.108489.
Sijiao Wang 1 Linjing Gong 2 Yuqing Mo 1 Jun Zhang 1 Zhilong Jiang 1 Zhengan Tian 3 Changzhou Shao 4
Affiliations

Affiliations

  • 1 Department of Pulmonary Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
  • 2 Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
  • 3 Shanghai International Travel Health Care Center, Shanghai 200335, China.
  • 4 Department of Pulmonary Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of Pulmonary Medicine, Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen 361015, China. Electronic address: sczzhongshan@126.com.
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-β 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.

Keywords

Allergic lung disease; Apoptosis; Aspergillus fumigatus; Endoplasmic reticulum stress; Resveratrol.

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