Treatment with 1,25(OH)2D3 induced HDAC2 expression and reduced NF-κB p65 expression in a rat model of OVA-induced asthma.
Recent evidence indicates that a deficiency of 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) may influence asthma pathogenesis; however, its roles in regulating specific molecular transcription mechanisms remain unclear. We aimed to investigate the effect of 1,25(OH)2D3 on the expression and enzyme activity of histone deacetylase 2 (HDAC2) and its synergistic effects with dexamethasone (Dx) in the inhibition of inflammatory cytokine secretion in a rat asthma model. Healthy Wistar rats were randomly divided into 6 groups: control, asthma, 1,25(OH)2D3 pretreatment, 1,25(OH)2D3 treatment, Dx treatment, and Dx and 1,25(OH)2D3 treatment. Pulmonary inflammation was induced by ovalbumin (OVA) sensitization and challenge (OVA/OVA). Inflammatory cells and cytokines in the bronchoalveolar lavage (BAL) fluid and histological changes in lung tissue were examined. Nuclear factor kappa B (NF-κB) p65 and HDAC2 expression levels were assessed with Western blot analyses and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). Enzyme activity measurements and immunohistochemical detection of HDAC2 were also performed. Our data demonstrated that 1,25(OH)2D3 reduced the airway inflammatory response and the level of inflammatory cytokines in BAL. Although NF-κB p65 expression was attenuated in the pretreatment and treatment groups, the expression and enzyme activity of HDAC2 were increased. In addition, 1,25(OH)2D3 and Dx had synergistic effects on the suppression of total cell infusion, cytokine release, and NF-κB p65 expression, and they also increased HDAC2 expression and activity in OVA/OVA rats. Collectively, our results indicated that 1,25(OH)2D3 might be useful as a novel HDAC2 activator in the treatment of asthma.
Department of Gerontology Medicine, Xinhua Hospital, Shanghai Jiatong University School of Medicine, Shanghai, China.
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Zhou
Department of Gerontology Medicine, Xinhua Hospital, Shanghai Jiatong University School of Medicine, Shanghai, China.
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Wang
Department of Gerontology Medicine, Xinhua Hospital, Shanghai Jiatong University School of Medicine, Shanghai, China.
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Yang
Department of Gerontology Medicine, Xinhua Hospital, Shanghai Jiatong University School of Medicine, Shanghai, China.
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Liu
Department of Gerontology Medicine, Xinhua Hospital, Shanghai Jiatong University School of Medicine, Shanghai, China.
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Kang
Department of Gerontology Medicine, Xinhua Hospital, Shanghai Jiatong University School of Medicine, Shanghai, China.
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Wang
Department of Gerontology Medicine, Xinhua Hospital, Shanghai Jiatong University School of Medicine, Shanghai, China.
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Gu
Department of Gerontology Medicine, Xinhua Hospital, Shanghai Jiatong University School of Medicine, Shanghai, China.
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Wang
D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy*; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002117:Calcitriol / Q000494:pharmacology* / Q000627:therapeutic use; D002452:Cell Count; D016207:Cytokines / Q000032:analysis / Q000187:drug effects; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D056464:Histone Deacetylase 2 / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D008168:Lung / Q000737:chemistry / Q000187:drug effects; D008297:Male; D016328:NF-kappa B / Q000032:analysis / Q000187:drug effects*; D010047:Ovalbumin; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D016896:Treatment Outcome; D014815:Vitamins / Q000494:pharmacology* / Q000627:therapeutic use
D016207:Cytokines; D016328:NF-kappa B; D014815:Vitamins; D010047:Ovalbumin; C533426:Hdac2 protein, rat; D056464:Histone Deacetylase 2; D002117:Calcitriol