Role of Vitamin D3 Up-regulated Protein 1(VDUP1) in Mouse Asthma Model

Abstract

Vitamin D3 upregulated protein 1 (VDUP1) is a multifunctional protein that is mainly distributed in immune organs and can exacerbate tumorigenesis and chronic inflammation, it may be related to an increase of immune-mediated materials such as proinflammatory cytokines, lymphokines, and transcription factors. In asthma, several cytokines have been reported to be involved in the inflammatory process. Here, we evaluated the effect of a lack of VDUP1 in ovalbumin (OVA)-induced airway inflammation in a mouse model of asthma. VDUP1 -/-(KO) and wild type (WT) mice were sensitized to OVA by intraperitoneal injection, and challenged with repeated exposure to OVA using an ultrasonic nebulizer. To investigate the difference between the groups, airway hyperresponsiveness (AHR), inflammatory cell number, and immunoglobulin E levels in bronchoalveolar lavage fluid (BALF), histopathological lesions (H&E stain), immunohistochemistry using inducible nitric oxide synthase (iNOS) antibody. And real-time polymerase chain reaction (PCR) using messenger RNA (mRNA) from lung tissue was analyzed. AHR, infiltration of leukocytes into the lung, total number of leukocytes recovered in BALF, and mucus secretion by goblet cells in bronchus were aggravated in KO/OVA mice compared with WT/OVA mice. The IgE level of BALF from KO/OVA treated mice was higher than that of WT/OVA mice. In lung sections, there was higher iNOS staining intensity in KO/OVA mice than WT/OVA mice. In addition, the mRNA of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-4, IL-1β, and iNOS increased in KO/OVA treated mice compared with WT/OVA mice. Depletion of VDUP1 aggravated the development of allergic airway inflammation and hyperresponsiveness possibly through various cytokines involved in VDUP1.