2. Academic Validation
  3. Pirfenidone and nintedanib attenuates pulmonary artery endothelial and smooth muscle cells transformations induced by IL-11

Pirfenidone and nintedanib attenuates pulmonary artery endothelial and smooth muscle cells transformations induced by IL-11

  • Eur J Pharmacol. 2024 Jun 5:972:176547. doi: 10.1016/j.ejphar.2024.176547.
Inés Roger 1,  Paula Montero 2,  Javier Milara 3,  Julio Cortijo 4
Affiliations

Affiliations

  • 1 Biomedical Research Networking Centre on Respiratory Diseases (CIBERES), Health Institute Carlos III, 28029, Madrid, Spain; Department of Pharmacology, Faculty of Medicine, University of Valencia, 46010, Valencia, Spain; Faculty of Health Sciences, Universidad Europea de Valencia, 46010, Valencia, Spain. Electronic address: ines.roger@universidad.europea.es.
  • 2 Biomedical Research Networking Centre on Respiratory Diseases (CIBERES), Health Institute Carlos III, 28029, Madrid, Spain; Department of Pharmacology, Faculty of Medicine, University of Valencia, 46010, Valencia, Spain; Faculty of Health Sciences, Universidad Europea de Valencia, 46010, Valencia, Spain.
  • 3 Biomedical Research Networking Centre on Respiratory Diseases (CIBERES), Health Institute Carlos III, 28029, Madrid, Spain; Department of Pharmacology, Faculty of Medicine, University of Valencia, 46010, Valencia, Spain; Pharmacy Unit, University General Hospital Consortium, 46014, Valencia, Spain.
  • 4 Biomedical Research Networking Centre on Respiratory Diseases (CIBERES), Health Institute Carlos III, 28029, Madrid, Spain; Department of Pharmacology, Faculty of Medicine, University of Valencia, 46010, Valencia, Spain; Research and Teaching Unit, University General Hospital Consortium, 46014, Valencia, Spain.
PMID: 38561103 DOI: 10.1016/j.ejphar.2024.176547
Abstract

Idiopathic pulmonary fibrosis (IPF) associated to pulmonary hypertension (PH) portends a poor prognosis, characterized by lung parenchyma fibrosis and pulmonary artery remodeling. Serum and parenchyma levels of Interleukin 11 (IL-11) are elevated in IPF-PH patients and contributes to pulmonary artery remodeling and PH. However, the effect of current approved therapies against IPF in pulmonary artery remodeling induced by IL-11 is unknown. The aim of this study is to analyze the effects of nintedanib and pirfenidone on pulmonary artery endothelial and smooth muscle cell remodeling induced by IL-11 in vitro. Our results show that nintedanib (NTD) and pirfenidone (PFD) ameliorates endothelial to mesenchymal transition (EnMT), pulmonary artery smooth muscle cell to myofibroblast-like transformation and pulmonary remodeling in precision lung cut slices. This study provided also evidence of the inhibitory effect of PFD and NTD on IL-11-induced endothelial and muscle cells proliferation and senescence. The inhibitory effect of these drugs on monocyte arrest and angiogenesis was also studied. Finally, we observed that IL-11 induced canonical signal transducer and activator of transcription 3 (STAT3) and non-canonical mitogen-activated protein kinase 1/2 (ERK1/2) phosphorylation, but, PFD and NTD only inhibited ERK1/2 phosphorylation. Therefore, this study provided evidence of the inhibitory effect of NTD and PFD on markers of pulmonary artery remodeling induced by IL-11.

Keywords

IL-11; Idiopathic pulmonary fibrosis; Nintedanib; Pirfenidone; Pulmonary artery endothelial cells; Pulmonary artery smooth muscle cells; Pulmonary hypertension.

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