VitA or VitD ameliorates bronchopulmonary dysplasia by regulating the balance between M1 and M2 macrophages

Abstract

Purpose: To investigate the therapeutic effects of vitamin A (VitA) or vitamin D (VitD) against bronchopulmonary dysplasia (BPD) and the underlying mechanism from the perspective of macrophage polarization. Methods: A BPD model was established on rats. Hematoxylin and eosin staining was used to evaluate the pathological state of lung tissues. The expression of CD68 was determined by immunohistochemistry assay. The infiltration of M1 and M2 macrophages was marked by immunofluorescence. The expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-10, nitric oxide synthase (NOS), and arginase-1 (Arg-1) were evaluated by quantitative reverse transcription polymerase chain reaction assay, and the ratio of M1/M2 in the bronchoalveolar lavage fluid was determined by flow cytometry. Results: Disordered alveolar structure in the lung tissue, thickened alveolar septa, and infiltration of inflammatory cells around the alveolar cavity and pulmonary septa were observed in lipopolysaccharide (LPS)-treated rats. On day 21 post-natal (PN21), the pathological state was aggravated, alveolar simplification was observed, and the expression level of CD68 in the lung tissues was significantly elevated, and these results were dramatically alleviated in the VitA, VitD, and VitA+VitD groups. However, no significant synergistic effect was observed between VitA+VitD and VitA or VitD groups. After the administration with VitA or VitD, IL-10 and Arg-1 were up-regulated on PN10. TNF-α and NOS were up-regulated on PN21. The ratio of macrophage polarization and M2 macrophages increased considerably after the stimulation with LPS, and this result was significantly reversed by VitA or VitD. A significant difference was observed on the effect of different dosages of VitA or VitD on macrophage polarization, among which moderate dosages of VitA or VitD exerted the most significant influence on macrophage polarization. Conclusion: The BPD-linked pulmonary injury stimulated by LPS can be ameliorated by the introduction of VitA or VitD.

Keywords

• Vitamin A
• Vitamin D
• Bronchopulmonary dysplasia
• M1 macrophages
• M2 macrophages