Effects of calcitriol (1, 25-dihydroxy-vitamin D3) on the inflammatory response induced by H9N2 influenza virus infection in human lung A549 epithelial cells and in mice

Gui, Boxiang; Chen, Qin; Hu, Chuanxia; Zhu, Chengshen; He, Guimei

doi:10.1186/s12985-017-0683-y

Cited by 44 publications

(38 citation statements)

References 37 publications

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“…This has led to mixed results, most likely because oral supplementation can only increase serum 25(OH)D 3 levels (and tissue levels of 1,25(OH) 2 D 3 ) to a limited degree. Similarly, Gui et al showed that while systemic administration of 1,25(OH) 2 D 3 (by daily intraperitoneal injection over 2 weeks) initially led to reduced inflammation, there were negative effects in the long term. Therefore, we wished to examine the potential for topical administration of vitamin D to the oral cavity.…”

Section: Introductionmentioning

confidence: 93%

Activation of vitamin D in the gingival epithelium and its role in gingival inflammation and alveolar bone loss

Menzel

Ruddick

Chowdhury

et al. 2019

J of Periodontal Research

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Background and Objective Both chronic and aggressive periodontal disease are associated with vitamin D deficiency. The active form of vitamin D, 1,25(OH)2D3, induces the expression of the antimicrobial peptide LL‐37 and innate immune mediators in cultured human gingival epithelial cells (GECs). The aim of this study was to further delineate the mechanism by which vitamin D enhances the innate defense against the development of periodontal disease (PD). Materials and Methods Wild‐type C57Bl/6 mice were made deficient in vitamin D by dietary restriction. Cultured primary and immortalized GEC were stimulated with 1,25(OH)2D3, followed by infection with Porphyromonas gingivalis, and viable intracellular bacteria were quantified. Conversion of vitamin D3 to 25(OH)D3 and 1,25(OH)2D3 was quantified by ELISA. Effect of vitamin D on basal IL‐1α expression in mice was determined by topical administration to the gingiva of wild‐type mice, followed by qRT‐PCR. Results Dietary restriction of vitamin D led to alveolar bone loss and increased inflammation in the gingiva in the mouse model. In primary human GEC and established human cell lines, treatment of GEC with 1,25(OH)2D3 inhibited the intracellular growth of P. gingivalis. Cultured GEC expressed two 25‐hydroxylases (CYP27A1 and CYP2R1), as well as 1‐α hydroxylase, enabling conversion of vitamin D to both 25(OH)D3 and 1,25(OH)2D3. Topical application of both vitamin D3 and 1,25(OH)2D3 to the gingiva of mice led to rapid inhibition of IL‐1α expression, a prominent pro‐inflammatory cytokine associated with inflammation, which also exhibited more than a 2‐fold decrease from basal levels in OKF6/TERT1 cells upon 1,25(OH)2D3 treatment, as determined by RNA‐seq. Conclusion Vitamin D deficiency in mice contributes to PD, recapitulating the association seen in humans, and provides a unique model to study the development of PD. Vitamin D increases the activity of GEC against the invasion of periodontal pathogens and inhibits the inflammatory response, both in vitro and in vivo. GEC can convert inactive vitamin D to the active form in situ, supporting the hypothesis that vitamin D can be applied directly to the gingiva to prevent or treat periodontal disease.

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Section: Introductionmentioning

confidence: 93%

Activation of vitamin D in the gingival epithelium and its role in gingival inflammation and alveolar bone loss

Menzel

Ruddick

Chowdhury

et al. 2019

J of Periodontal Research

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“…In a lung epithelial cell study, calcitriol treatment prior to and post infection with H9N2 influenza significantly decreased expression of the influenza M gene, IL-6, and IFN-β in A549 cells, but did not affect virus replication. [113] RSV Demonstrated that the human cathelicidin LL-37 has effective antiviral activity against RSV in vitro and prevented virus-induced cell death in epithelial cultures, [114] RSV Performed a laboratory study that identified the mechanism by which vitamin D reduced risk of RSV.…”

Section: Clinical and Epidemiological Findings Regarding Covid-19mentioning

confidence: 99%

Evidence That Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths

Grant

Lahore

McDonnell

et al. 2020

Preprint

432

595

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The world is in the grips of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increase concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D [25(OH)D] concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome, and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/ml (100–150 nmol/l). For treatment of people who become infected with COVID-19, higher vitamin D3 doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.

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“…PAMs were infected with SIV (MOI: 0.1) and were then treated with various concentrations of AFB 1 for 48 h because the viral titers peaked at 48 hpi and then plateaued [33]. As shown in Fig.…”

Section: Low Concentrations Of Afb 1 Promote Siv Infection In Pamsmentioning

confidence: 99%

Low-Level Aflatoxin B1 Promotes Influenza Infection and Modulates a Switch in Macrophage Polarization from M1 to M2

Sun

Liu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Swine influenza virus (SIV) is a major pathogen of both animals and humans. Afatoxin B1 (AFB₁) is one of the most common mycotoxins in feed and food. However, the central contribution of AFB₁ to SIV infection remains unclear. Methods: Here, TCID₅₀ assays, fluorescence-based quantitative real-time PCR, western blotting, immunofluorescence staining, histopathological examination, flow cytometry and scanning electron microscopy were performed to investigate the involvement and underlying mechanism of AFB₁ in SIV infection in vivo and in vitro using mouse models and porcine alveolar macrophage (PAM) models, respectively. Results: The in vivo study showed that low levels of AFB₁ promoted SIV infection and increased its severity, as demonstrated by the increased mRNA expression of viral matrix protein (M); by the increased protein expression of nucleoprotein (NP), matrix protein 1 and ion channel protein; and by animal weight loss, lung index and lung histologic damage. In addition, the increased occurrence of SIV infection accompanied by increases in the level of IL-10 in sera and lungs, in the spleen index and in the number of CD206-positive mouse alveolar macrophages but decreases in the level of TNF-α in sera and lungs, in the thymus index and in the number of CD80-positive mouse alveolar macrophages was observed in SIV-infected mice after low-level AFB₁ exposure. The in vitro study showed that low concentrations of AFB₁ promoted SIV infection, as demonstrated by the increases in viral titers and viral M mRNA and NP expression levels in SIV-infected PAMs as well as by the number of cells positive for NP protein expression. Furthermore, AFB₁ promoted the polarization of SIV-infected PAMs to the M1 phenotype at 8 hpi and to the M2 phenotype at 24 hpi, as measured by the increases in IL-10 expression and in the number of CD206-positive PAMs as well as by the morphological changes observed by scanning electron microscopy. The administration of the immune stimulant lipopolysaccharide (LPS) reversed the switch in PAM polarization from M2 to M1 and thereby counteracted the promotion of influenza virus infection induced by AFB₁. Conclusion: Our results are the first to confirm that low-level exposure to AFB₁ promotes SIV infection and modulates a switch in macrophage polarization from M1 to M2. The work reported here provides important data that point to a role for AFB₁ in SIV infection, and it opens a new field of study.

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Effects of calcitriol (1, 25-dihydroxy-vitamin D3) on the inflammatory response induced by H9N2 influenza virus infection in human lung A549 epithelial cells and in mice

Cited by 44 publications

References 37 publications

Activation of vitamin D in the gingival epithelium and its role in gingival inflammation and alveolar bone loss

Activation of vitamin D in the gingival epithelium and its role in gingival inflammation and alveolar bone loss

Evidence That Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths

Low-Level Aflatoxin B1 Promotes Influenza Infection and Modulates a Switch in Macrophage Polarization from M1 to M2

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