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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2018.01276

Celastrol Alleviates Chronic obstructive pulmonary disease by Inhibiting Cellular Inflammation Induced by Cigarette Smoke via the Ednrb/Kng1 Signaling Pathway

 Qiong Chen1, 2*, Ke Shi1, 2, Xi Chen3,  Bin Xie2, Sha S. Yang2, Da Liu2 and Gan Dai4
  • 1National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, China
  • 2Department of Geriatrics, Xiangya Hospital, Central South University, China
  • 3Xiangya Hospital, Central South University, China
  • 4Xiangya School of Medicine, Central South University, China

Chronic obstructive pulmonary disease (COPD) is a debilitating disease caused by chronic exposure to cigarette smoke (CS). Celastrol is a pentacyclic triterpenoid compound exhibits potent antioxidant and anti-inflammatory activities. Also it is presently known to protect against liver damage induced by type II diabetes. However, its role in COPD is unclear. In this study, we investigated the effects of Celastrol on cellular inflammation in mice exposed to CS and Beas-2B cells treated with CS extract (CSE). C57BL/6 mice and Beas-2B cells were randomly divided into three groups: control group, COPD or CSE group, and Celastrol treatment group. The COPD mice models were subjected to smoke exposure and cell models were treated with CSE. Bioinformatics analysis was performed to identify differentially expressed genes following treatment with Celastrol in COPD, the molecular networks was mapped by Cytoscape. The levels of inflammatory cytokines interleukin-10, monocyte chemoattractant protein-1, and oxidative stress factors superoxide dismutase and catalase were measured by enzyme-linked immunosorbent assay. Hematoxylin and eosin staining to detect the injury of mouse lung tissue. mRNA and protein levels of Ednrb and Kng1 in the tissues and cells were measured by quantitative polymerase chain reaction (PCR) and western blotting, respectively. Apoptosis was measured by flow cytometry and TUNEL staining. Compared to mice in the COPD group, mice treated with Celastrol had significantly reduced levels of inflammatory cytokines interleukin-10 and monocyte chemoattractant protein-1 in the serum and bronchoalveolar lavage fluid, and significantly increased levels of oxidative stress factors superoxide dismutase and catalase. The same results were obtained at the cellular level using Beas-2B cells. Compared to the model groups, Celastrol reduced lung injury in mice and significantly reduced cellular apoptosis. Bioinformatics analysis showed that Ednrb is a target gene of Celastrol and differentially expressed in COPD. Quantitative PCR analysis showed that Ednrb expression in patients with COPD was significantly increased compared to that in healthy controls. Additionally, Celastrol effectively reduced Ednrb/Kng1 expression in both cell and animal models. Celastrol has a therapeutic effect on COPD and may alleviate COPD by inhibiting inflammation development by suppressing the Ednrb/Kng1 signaling pathway.

Keywords: EDNRB, Kng1, chronic obstructive pulmonary disease, Cigarette smoke exposure, Inflammation, Celastrol

Received: 15 Aug 2018; Accepted: 18 Oct 2018.

Edited by:

Mohamed M. Abdel-Daim, Suez Canal University, Egypt

Reviewed by:

SHEILA LEONE, Università degli Studi G. d'Annunzio Chieti e Pescara, Italy
Jian Zhang, Tianjin Medical University, China
Yasmina M. Abd EL-Hakim, Faculty of Veterinary Medicine, Zagazig University, Egypt  

Copyright: © 2018 Chen, Shi, Chen, Xie, Yang, Liu and Dai. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mr. Qiong Chen, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China,