Maternal vitamin D deficiency impairs Treg and Breg responses in offspring mice and deteriorates allergic airway inflammation

Huang, Fei; Ju, Yang-hua; Wang, Hongbo; Li, Yanan

doi:10.1186/s13223-020-00487-1

Cited by 7 publications

(6 citation statements)

References 40 publications

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“… 39 Low levels of VitD observed in the plasma of newborn mice caused the deterioration of allergic airway inflammation, suggesting that VitD deficiency affected inflammation. 40 It has been demonstrated that VitD deficiency contributes to lung fibrosis, and VitD supplementation combined with anti-fibrotic therapeutics can ameliorate this symptom. 41 , 42 Previous research has frequently shown the anti-inflammatory effects of VitD in some human diseases, implicating VitD as a possible anti-inflammation therapy.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D Ameliorates Apoptosis and Inflammation by Targeting the Mitochondrial and MEK1/2-ERK1/2 Pathways in Hyperoxia-Induced Bronchopulmonary Dysplasia

Hu¹,

Wu²,

Wang³

et al. 2022

JIR

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Bronchopulmonary dysplasia (BPD) is a common and severe complication in preterm infants. Vitamin D (VitD) has been reported to protect against BPD; however, its role in the mitochondria-mediated and MEK1/2-ERK1/2 pathways has not yet been reported. Methods: We first performed in vivo studies using neonatal C57BL/6 mice in which we induced BPD by exposing them to a hyperoxic environment (85% O 2 ). The mice were divided into room air (RA; 21% O 2 ), RA+VitD, BPD, and BPD+VitD groups. Hematoxylin and eosin and Masson's trichrome staining were used to evaluate lung injury. Inflammation and apoptosis were measured using ELISA, RT-qPCR, and TUNEL assays. We then analyzed BEAS-2B cells divided into the same groups along with an additional BPD+VitD+inhibitor group. Mitochondrial apoptosis was evaluated by transmission electron microscopy, mitochondrial membrane potential, and Western blotting. We then used VDR-shRNA to silence the Vitamin D Receptor (VDR) in the BEAS-2B cells. The inflammation, apoptotic rate, and the phosphorylated forms of MEK1/2 and ERK1/2 in cells were detected by RT-qPCR, flow cytometry, and Western blotting. Results: The mean linear intercept, septal thickness, and abnormal fibrosis increased, while radial alveolar count decreased in BPD lungs compared to RA lungs. VitD administration was able to ameliorate the phenotype in BPD lungs. IL-6, IFN-γ, and TNF-α expression and the apoptotic rate decreased in the BPD+VitD lung group. VitD pretreatment restored abnormal mitochondrial morphology, reduced mitochondrial membrane loss, and reduced the expression of cleaved caspase-3, Bax, and Bcl-2 in BEAS-2B cells. VitD administration also reduced IL-6, IFN-γ, and TNF-α mRNA, as well as pMEK1/2 and pERK1/2 expression and apoptosis rate in cells exposed to hyperoxia. Conclusion:We concluded that VitD treatment ameliorated apoptosis and inflammation by targeting the mitochondrial pathway and via the MEK1/2-ERK1/2 signaling pathway in BPD, thus supporting its potential therapeutic use in this condition.

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Section: Discussionmentioning

confidence: 99%

Vitamin D Ameliorates Apoptosis and Inflammation by Targeting the Mitochondrial and MEK1/2-ERK1/2 Pathways in Hyperoxia-Induced Bronchopulmonary Dysplasia

Hu¹,

Wu²,

Wang³

et al. 2022

JIR

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“…Here, vitamin D is also important for maintaining healthy gut microbiota and the activation of Tregs [120,121].…”

Section: Intestinal Disorders and Gut Microbiotamentioning

confidence: 99%

“…In addition, it is intriguing that the consumption of raisins is reported to induce beneficial changes in gut microbiota [119]. Here, vitamin D is also important for maintaining healthy gut microbiota and the activation of Tregs [120,121]. High-fat, high-sugar and high-calorie diet causes obesity; without sufficient exercise, people tend to the onset of metabolic syndrome.…”

Section: Intestinal Disorders and Gut Microbiotamentioning

confidence: 99%

Phytochemicals and Vitamin D for a Healthy Life and Prevention of Diseases

Santa

Watanabe

Kumazawa

et al. 2023

IJMS

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A variety of phytocompounds contained in medical plants have been used as medication, including Kampo (traditional Japanese) medicine. Phytochemicals are one category of the chemical compounds mainly known as antioxidants, and recently, their anti-inflammatory effects in preventing chronic inflammation have received much attention. Here, we present a narrative review of the health-promotion and disease-prevention effects of phytochemicals, including polyphenols, the latter of which are abundant in onions, oranges, tea, soybeans, turmeric, cacao, and grapes, along with the synergetic effects of vitamin D. A phenomenon currently gaining popularity in Japan is finding non-disease conditions, so-called ME-BYO (mibyou) and treating them before they develop into illnesses. In addition to lifestyle-related diseases such as metabolic syndrome and obesity, dementia and frailty, commonly found in the elderly, are included as underlying conditions. These conditions are typically induced by chronic inflammation and might result in multiple organ failure or cancer if left untreated. Maintaining gut microbiota is important for suppressing (recently increasing) intestinal disorders and for upregulating immunity. During the COVID-19 pandemic, the interest in phytochemicals and vitamin D for disease prevention increased, as viral and bacterial infection to the lung causes fatal inflammation, and chronic inflammation induces pulmonary fibrosis. Furthermore, sepsis is a disorder inducing severe organ failure by the infection of microbes, with a high mortality ratio in non-coronary ICUs. However, antimicrobial peptides (AMPs) working using natural immunity suppress sepsis at the early stage. The intake of phytochemicals and vitamin D enhances anti-inflammatory effects, upregulates immunity, and reduces the risk of chronic disorders by means of keeping healthy gut microbiota. Evidence acquired during the COVID-19 pandemic revealed that daily improvement and prevention of underlying conditions, in terms of lifestyle-related diseases, is very important because they increase the risk of infectious diseases. This narrative review discusses the importance of the intake of phytochemicals and vitamin D for a healthy lifestyle and the prevention of ME-BYO, non-disease conditions.

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“…10 Specific inflammatory T helper 17 (Th17) cells play a crucial role in the pathogenesis of airway inflammation. 11 A regulatory T (Treg) cell response is vital in the inflammation resolution response. 12 The cells undergo terminal differentiation to elicit conflicting functions with Th17 cells to induce inflammation whereas Treg cells inhibit this phenomenon.…”

mentioning

confidence: 99%

“…12 The cells undergo terminal differentiation to elicit conflicting functions with Th17 cells to induce inflammation whereas Treg cells inhibit this phenomenon. 11,13 Therefore, the balance of the Th17/Treg is critical in the inflammatory response to ameliorate lung inflammation by a uniform balance of Th17/Treg. 14,15 A deficiency of vitamin D can impede the downregulation of Th17 cells and the upregulation of Treg cells, thus unbalancing the proportion of Th17/Treg.…”

mentioning

confidence: 99%

Vitamin D has an effect on airway inflammation and Th17/Treg balance in asthmatic mice

Xiao

et al. 2021

The Kaohsiung J of Med Scie

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Asthma is regarded as a chronic inflammation of the airway. Research has highlighted the significance of Vitamin D in asthma. This study explored the mechanism of vitamin D on asthma. The asthma mouse model was established by ovalbumin (OVA) sensitization and treated with vitamin D (50 or 100 ng/ml). The morphological changes of the airway were observed by HE staining. The serum IgE contents and MDA, ROS, and SOD expressions in the bronchoalveolar lavage fluid (BALF) were detected by ELISA. The Th17 and Treg cells were detected using flow cytometry. The RORγt and Foxp 3 expressions were detected by Reverse transcription quantitative polymerase chain reaction (RT-qPCR). IL-17, IL-10, and TGF-β1 expressions were detected using ELISA. The NF-κB pathway was blocked using the NF-κB pathway inhibitor, Andrographolide sulfonate. The NF-κB pathway-related indexes were detected by western blotting. After blockade of the NF-κB pathway, the IL-17, IL-10, and TGF-G1 expressions were detected. OVAsensitized asthma induced airway remodeling and elevated IgE content in mice, which was downregulated after vitamin D treatment. MDA and ROS were upregulated and SOD was downregulated in asthmatic mice, while vitamin D inverted the changes. Th17/Treg ratio was imbalanced, RORγt and IL-17 were upregulated, and Foxp 3, IL-10, and TGF-β1 were downregulated after OVA sensitization, while vitamin D treatment inverted these changes and inhibited the NF-κB-p65 phosphorylation level. After blockade of the NF-κB pathway, IL-17 was downregulated and IL-10 and TGF-β1 were upregulated. In conclusion, vitamin D rectified the Th17/Treg balance and alleviated airway inflammation by inhibiting the NF-κB pathway in asthmatic mice.

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Maternal vitamin D deficiency impairs Treg and Breg responses in offspring mice and deteriorates allergic airway inflammation

Cited by 7 publications

References 40 publications

Vitamin D Ameliorates Apoptosis and Inflammation by Targeting the Mitochondrial and MEK1/2-ERK1/2 Pathways in Hyperoxia-Induced Bronchopulmonary Dysplasia

Vitamin D Ameliorates Apoptosis and Inflammation by Targeting the Mitochondrial and MEK1/2-ERK1/2 Pathways in Hyperoxia-Induced Bronchopulmonary Dysplasia

Phytochemicals and Vitamin D for a Healthy Life and Prevention of Diseases

Vitamin D has an effect on airway inflammation and Th17/Treg balance in asthmatic mice

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