Inhibiting ATG5 mediated autophagy to regulate endoplasmic reticulum stress and CD4+ T lymphocyte differentiation: Mechanisms of acupuncture's effects on asthma.

Abstract

OBJECTIVE:

Asthma is characterized by airway hyperresponsiveness(AHR), inflammation and remodeling. Autophagy and endoplasmic reticulum stress(ERS) are dysregulated in asthma, and ATG5 has attracted wide attentions a representative gene of autophagy. Previous evidence shows that acupuncture may treat asthma by regulating the immune environment.However,the precise mechanism involved in acupuncture's effects on asthma is unclear. Thus, we investigated the inner-relationships of acupuncture and ATG5-mediated autophagy, ERS and CD4+ T lymphocyte differentiation in asthma.

METHODS:

Ovalbumin (OVA)-sensitized and challenged ATG5+/- and ATG5-/-mice with asthma were treated by acupuncture at Dazhui(GV14),Feishu(BL13) and Zusanli(ST36),and sacrificed the next day.Then blood and bronchoalveolar lavage fluid (BALF)samples were collected to determine inflammatory cell counts and cytokine levels. Lung tissue samples were obtained for histological examination, and the spleen was harvested for flow cytometry.

RESULTS:

Compared with the untreated group, acupuncture decreased BALF inflammatory cell counts and AHR in OVA-induced mice.Acupuncture decreased autophagy-related protein and mRNA (ATG5,Beclin-1,p62 and LC3B)amounts and ERS-related protein (p-PERK, p-IRE-1,Grp78, and ATF6)levels as well as autophagosome formation in lung tissue, concomitant with increased IFN-γ and decreased IL-4, IL-17 and TGF-β amounts in BALF.Consistently, the imbalance of CD4+ T lymphocyte subsets(Th1/Th2 and Treg/Th17) was also corrected by acupuncture.Meanwhile, AHR and inflammation were decreased in ATG5-/- mice compared with ATG+/-animals,without affecting the therapeutic effect of acupuncture.

CONCLUSION:

Acupuncture reduces airway inflammation and AHR in asthma by inhibiting ATG5-mediated autophagy to regulate endoplasmic reticulum stress and CD4+T lymphocyte differentiation.

• Authors: Huanyi Zhao, Fang Dong, Yuhui Li, Xiaojie Ren, Zhengyuan Xia, Yong Wang, Wuhua Ma
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 142 Pg. 112045 (Oct 2021) ISSN: 1950-6007 [Electronic] France
• PMID: 34426257 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Atg5 protein, mouse
• Autophagy-Related Protein 5
• Cytokines
• Ovalbumin

Topics

• Acupuncture Therapy
• Animals
• Asthma (chemically induced, immunology, pathology, therapy)
• Autophagosomes (ultrastructure)
• Autophagy (genetics, immunology)
• Autophagy-Related Protein 5 (antagonists & inhibitors, genetics, immunology)
• Bronchoalveolar Lavage Fluid (cytology, immunology)
• CD4-Positive T-Lymphocytes (cytology, immunology)
• Cell Differentiation (immunology)
• Cytokines (metabolism)
• Disease Models, Animal
• Endoplasmic Reticulum Stress (genetics, immunology)
• Female
• Inflammation (genetics, immunology)
• Mice, Inbred C57BL
• Ovalbumin (toxicity)
• Respiratory Hypersensitivity
• Mice