COVID-19 Research Paper Volume 14, Issue 3 pp 1110—1127
Dihydroartemisinin attenuates pulmonary inflammation and fibrosis in rats by suppressing JAK2/STAT3 signaling
- 1 Department of Gastrointestinal Surgery, Taizhou Clinical Medical School of Nanjing Medical University (Taizhou People’s Hospital), Taizhou 225300, Jiangsu, China
- 2 Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210009, Jiangsu, China
- 3 Department of Central Laboratory, Taizhou Clinical Medical School of Nanjing Medical University (Taizhou People’s Hospital), Taizhou 225300, Jiangsu, China
- 4 Department of Respiratory Medicine, Taizhou Clinical Medical School of Nanjing Medical University (Taizhou People’s Hospital), Taizhou 225300, Jiangsu, China
- 5 Department of the Pathology, Taizhou Clinical Medical School of Nanjing Medical University (Taizhou People’s Hospital), Taizhou 225300, Jiangsu, China
- 6 Department of the Operation Room, Taizhou Clinical Medical School of Nanjing Medical University (Taizhou People’s Hospital), Taizhou 225300, Jiangsu, China
Received: July 19, 2021 Accepted: January 4, 2022 Published: February 4, 2022
https://doi.org/10.18632/aging.203874How to Cite
Copyright: © 2022 You et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has induced a worldwide pandemic since early 2020. COVID-19 causes pulmonary inflammation, secondary pulmonary fibrosis (PF); however, there are still no effective treatments for PF. The present study aimed to explore the inhibitory effect of dihydroartemisinin (DHA) on pulmonary inflammation and PF, and its molecular mechanism. Morphological changes and collagen deposition were analyzed using hematoxylin-eosin staining, Masson staining, and the hydroxyproline content. DHA attenuated early alveolar inflammation and later PF in a bleomycin-induced rat PF model, and inhibited the expression of interleukin (IL)-1β, IL-6, tumor necrosis factor α (TNFα), and chemokine (C-C Motif) Ligand 3 (CCL3) in model rat serum. Further molecular analysis revealed that both pulmonary inflammation and PF were associated with increased transforming growth factor-β1 (TGF-β1), Janus activated kinase 2 (JAK2), and signal transducer and activator 3(STAT3) expression in the lung tissues of model rats. DHA reduced the inflammatory response and PF in the lungs by suppressing TGF-β1, JAK2, phosphorylated (p)-JAK2, STAT3, and p-STAT3. Thus, DHA exerts therapeutic effects against bleomycin-induced pulmonary inflammation and PF by inhibiting JAK2-STAT3 activation. DHA inhibits alveolar inflammation, and attenuates lung injury and fibrosis, possibly representing a therapeutic candidate to treat PF associated with COVID-19.
Abbreviations
BLM: bleomycin; CCL3: chemokine (C-C Motif) Ligand 3; COVID-19: Coronavirus disease 2019; CT: Computed tomography; DHA: dihydroartemisinin; H&E: Hematoxylin-Eosin; IHC: Immunohistochemistry; IL: interleukin; IPF: idiopathic pulmonary fibrosis; JAK2: Janus activated kinase 2; PF: pulmonary fibrosis; STAT3: signal transducer and activator; TGF-β1: transforming growth factor-β1; TNFα: tumor necrosis factor α.