p14ARF ameliorates inflammation and airway remodeling in nitric acid aerosol inhalation-induced bronchiolitis obliterans.

Abstract

BACKGROUND:

To investigate the protective effect of p14ARF in a nitric acid (NA) aerosol inhalation-induced bronchiolitis obliterans (BO) mouse model and its potential regulatory mechanism.

METHODS:

A BO mouse model was established by NA aerosol inhalation. The expressions of p14ARF, phosphatidylinositol-3-kinase (PI3K), and protein kinase B (AKT) were detected by quantitative reverse transcription PCR (qRT-PCR) and western blot (WB). Hematoxylin (HE) staining, Masson staining, and periodic acid-Schiff (PAS) staining observed pulmonary histological changes. TdT-mediated dUTP nick end labeling (TUNEL) staining detected pulmonary cell apoptosis, and enzyme-linked immunosorbent assay (ELISA) measured matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), interleukon-6 (IL-6), and transforminh growth factor-β (TGF-β) levels in lung tissue and bronchoalveolar lavage fluid (BALF).

RESULTS:

The expressions of p14ARF, PI3K, and AKT showed a time gradient change, with a decrease trend (*P < 0.05 and **P < 0.01). Severe inflammatory infiltration and tracheal fibrosis were found in lung tissue in the modeling group (BO group) compared with the control group (Con group). The pH, PaO2, and PaO2/FiO2 values significantly reduced, while the PaCO2 value and the number of TUNEL-positive cells increased in BO group (P < 0.05). In addition, MMP-2, MMP-9, IL-6, and TGF-β levels remarkably increased, with an increase in the number of white blood cells, neutrophils, and lymphocytes in BO group (P < 0.05). Furthermore, p14ARF up-regulation reversed the trend of the aforementioned indexes in BO mice.

CONCLUSIONS:

p14ARF ameliorated the inflammatory response and airway remodeling in a BO mouse model via the PI3K/AKT pathway.

• Authors: Ting Yang, Chang Xu, Niu Ding, Shujuan Luo, Bichen Wu, Shijie Jin, Yanping Chen
• Journal: Experimental lung research (Exp Lung Res) Vol. 49 Issue 1 Pg. 27-38 ( 2023) ISSN: 1521-0499 [Electronic] England
• PMID: 36621972 (Publication Type: Journal Article)

Chemical References

• Matrix Metalloproteinase 2
• Proto-Oncogene Proteins c-akt
• Tumor Suppressor Protein p14ARF
• Nitric Acid
• Matrix Metalloproteinase 9
• Phosphatidylinositol 3-Kinases
• Tissue Inhibitor of Metalloproteinase-1
• Interleukin-6
• Transforming Growth Factor beta

Topics

• Mice
• Animals
• Matrix Metalloproteinase 2
• Proto-Oncogene Proteins c-akt (metabolism)
• Tumor Suppressor Protein p14ARF
• Nitric Acid
• Matrix Metalloproteinase 9 (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Airway Remodeling
• Tissue Inhibitor of Metalloproteinase-1 (metabolism)
• Interleukin-6
• Respiratory Aerosols and Droplets
• Bronchiolitis Obliterans (chemically induced, drug therapy, metabolism)
• Inflammation (drug therapy)
• Transforming Growth Factor beta
• Disease Models, Animal