2. Academic Validation
  3. Dopamine D1 receptor agonist alleviates acute lung injury via modulating inflammatory responses in macrophages and barrier function in airway epithelial cells

Dopamine D1 receptor agonist alleviates acute lung injury via modulating inflammatory responses in macrophages and barrier function in airway epithelial cells

  • Free Radic Biol Med. 2023 Mar 23;202:2-16. doi: 10.1016/j.freeradbiomed.2023.03.016.
Linlin Meng 1,  Muyun Wang 2,  Yixuan Gao 3,  Liangzhi Chen 4,  Kun Wang 2,  Wei Gao 5,  Qinghua Liu 6
Affiliations

Affiliations

  • 1 Shandong University of Traditional Chinese Medicine, Shandong, 250002, PR China; Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, PR China.
  • 2 Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, PR China.
  • 3 Department of Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, 250021, PR China.
  • 4 Shandong University of Traditional Chinese Medicine, Shandong, 250002, PR China.
  • 5 Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, PR China. Electronic address: grace19881118@126.com.
  • 6 Shandong University of Traditional Chinese Medicine, Shandong, 250002, PR China; Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, PR China. Electronic address: lzlqhlz@163.com.
PMID: 36965538 DOI: 10.1016/j.freeradbiomed.2023.03.016
Abstract

Acute lung injury (ALI) or its severe form, acute respiratory distress syndrome (ARDS) is a life-threatening illness without effective therapeutic interventions currently. Multiple lines of evidence indicated that overwhelming inflammatory responses and impaired epithelial barrier contributed to the pathogenesis of ALI/ARDS. Recently, dopamine (DA) system was identified to participate in various pulmonary diseases. Here, we discovered that dopamine D1-like receptors mainly expressed in macrophages and airway epithelial cells (AECs), which were downregulated by lipopolysaccharide (LPS) challenge in ALI mouse lung. SKF38393 (SKF) is a selective agonist for D1-like receptors and was demonstrated to inhibit excessive inflammatory responses and oxidative stress in THP-1 cell-derived macrophages and Beas-2B cells, as well as improve airway epithelial barrier dysfunction induced by LPS stimulation. Moreover, SKF administration could effectively decrease pulmonary inflammation, ameliorate tissue damage in the LPS-triggered ALI mice. The broad protective actions of SKF might be attributed to the activation of Nrf2 antioxidative system by use of the specific inhibitor, ML385. This study offers evidence of potent immunoregulatory activity of SKF in macrophages, AECs as well as ALI mouse model, which opens novel therapeutic avenues for the intervention of ALI/ARDS.

Keywords

Acute lung injury; Airway epithelial barrier; Dopamine receptors; Nrf2; Pulmonary macrophages; SKF38393.

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