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31 March 2020 : Animal Research  

Ibudilast, a Phosphodiesterase-4 Inhibitor, Ameliorates Acute Respiratory Distress Syndrome in Neonatal Mice by Alleviating Inflammation and Apoptosis

Dongjie Yang1CE, Yihan Yang2BDF, Yue Zhao3A*

DOI: 10.12659/MSM.922281

Med Sci Monit 2020; 26:e922281

Abstract

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a sudden and serious disease with increasing morbidity and mortality rates. Phosphodiesterase 4 (PDE4) is a novel target for inflammatory disease, and ibudilast (IBU), a PDE4 inhibitor, inhibits inflammatory response. Our study investigated the effect of IBU on the pathogenesis of neonatal ARDS and the underlying mechanism related to it.

MATERIAL AND METHODS: Western blotting was performed to analyze the expression levels of PDE4, CXCR4, SDF-1, CXCR5, CXCL1, inflammatory cytokines, and proteins related to cell apoptosis. Hematoxylin-eosin staining was performed to observe the pathological morphology of lung tissue. Pulmonary edema score was used to assess the degree of lung water accumulation after pulmonary injury. Enzyme-linked immunosorbent assay (ELISA) was used to assess levels of inflammatory factors (TNF-α, IL-1β, IL-6, and MCP-1) in serum. TUNEL assay was used to detect apoptotic cells.

RESULTS: Increased expression of PDE4 was observed in an LPS-induced neonatal ARDS mouse model, and IBU ameliorated LPS-induced pathological manifestations and pulmonary edema in lung tissue. In addition, IBU attenuated the secretion of inflammatory cytokines by inactivating the chemokine axis in the LPS-induced neonatal ARDS mouse model. Finally, IBU significantly reduced LPS-induced cell apoptosis in lung tissue.

CONCLUSIONS: IBU, a PDE4 inhibitor, protected against ARDS by interfering with pulmonary inflammation and apoptosis. Our findings provide a novel and promising strategy to regulate pulmonary inflammation in ARDS.

Keywords: Cyclic Nucleotide Phosphodiesterases, Type 4, severe acute respiratory syndrome

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Med Sci Monit 2021; 27:e935624

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750