scholarly journals Vitamin D Treatment Sequence Is Critical for Transcriptome Modulation of Immune Challenged Primary Human Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Henna-Riikka Malmberg ◽  
Andrea Hanel ◽  
Mari Taipale ◽  
Sami Heikkinen ◽  
Carsten Carlberg
Keyword(s):  
Vitamin D ◽  
Mononuclear Cells ◽  
Fungal Infections ◽  
Human Peripheral Blood ◽  
Active Form ◽  
Biologically Active ◽  
Treatment Sequence ◽  
Peripheral Blood Mononuclear ◽  
Lps Challenge ◽  
Immune Challenges

Microbe-associated molecular patterns, such as lipopolysaccharide (LPS) and β-glucan (BG), are surrogates of immune challenges like bacterial and fungal infections, respectively. The biologically active form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), supports the immune system in its fight against infections. This study investigated significant and prominent changes of the transcriptome of human peripheral blood mononuclear cells that immediately after isolation are exposed to 1,25(OH)2D3-modulated immune challenges over a time frame of 24-48 h. In this in vitro study design, most LPS and BG responsive genes are downregulated and their counts are drastically reduced when cells are treated 24 h after, 24 h before or in parallel with 1,25(OH)2D3. Interestingly, only a 1,25(OH)2D3 pre-treatment of the LPS challenge results in a majority of upregulated genes. Based on transcriptome-wide data both immune challenges display characteristic differences in responsive genes and their associated pathways, to which the actions of 1,25(OH)2D3 often oppose. The joined BG/1,25(OH)2D3 response is less sensitive to treatment sequence than that of LPS/1,25(OH)2D3. In conclusion, the functional consequences of immune challenges are significantly modulated by 1,25(OH)2D3 but largely depend on treatment sequence. This may suggest that a sufficient vitamin D status before an infection is more important than vitamin D supplementation afterwards.

scholarly journals Immunologic Effects of Vitamin D on Human Health and Disease

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 2097 ◽  
Author(s):  
Nipith Charoenngam ◽  
Michael F. Holick
Keyword(s):  
Vitamin D ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Active Form ◽  
Experimental Studies ◽  
Vitamin D Supplementation ◽  
Peripheral Blood Mononuclear ◽  
Hydroxyvitamin D ◽  
Increased Risk ◽  
25 Hydroxyvitamin D

Vitamin D is responsible for regulation of calcium and phosphate metabolism and maintaining a healthy mineralized skeleton. It is also known as an immunomodulatory hormone. Experimental studies have shown that 1,25-dihydroxyvitamin D, the active form of vitamin D, exerts immunologic activities on multiple components of the innate and adaptive immune system as well as endothelial membrane stability. Association between low levels of serum 25-hydroxyvitamin D and increased risk of developing several immune-related diseases and disorders, including psoriasis, type 1 diabetes, multiple sclerosis, rheumatoid arthritis, tuberculosis, sepsis, respiratory infection, and COVID-19, has been observed. Accordingly, a number of clinical trials aiming to determine the efficacy of administration of vitamin D and its metabolites for treatment of these diseases have been conducted with variable outcomes. Interestingly, recent evidence suggests that some individuals might benefit from vitamin D more or less than others as high inter-individual difference in broad gene expression in human peripheral blood mononuclear cells in response to vitamin D supplementation has been observed. Although it is still debatable what level of serum 25-hydroxyvitamin D is optimal, it is advisable to increase vitamin D intake and have sensible sunlight exposure to maintain serum 25-hydroxyvitamin D at least 30 ng/mL (75 nmol/L), and preferably at 40–60 ng/mL (100–150 nmol/L) to achieve the optimal overall health benefits of vitamin D.

scholarly journals Common and personal target genes of the micronutrient vitamin D in primary immune cells from human peripheral blood

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Andrea Hanel ◽  
Antonio Neme ◽  
Marjo Malinen ◽  
Emmi Hämäläinen ◽  
Henna-Riikka Malmberg ◽  
...  
Keyword(s):  
Vitamin D ◽  
Immune System ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Target Genes ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Active Form ◽  
Biologically Active ◽  
Expression Change

AbstractVitamin D is essential for the function of the immune system. In this study, we treated peripheral blood mononuclear cells (PBMCs) of healthy adults with the biologically active form of vitamin D3, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) using two different approaches: single repeats with PBMCs obtained from a cohort of 12 individuals and personalized analysis based on triplicates of five study participants. This identified 877 (cohort approach) and 3951 (personalized approach) genes that significantly (p < 0.05) changed their expression 24 h after 1,25(OH)2D3 stimulation. From these, 333 and 1232 were classified as supertargets, a third of which were identified as novel. Individuals differed largely in their vitamin D response not only by the magnitude of expression change but also by their personal selection of (super)target genes. Functional analysis of the target genes suggested the overarching role of vitamin D in the regulation of metabolism, proliferation and differentiation, but in particular in the control of functions mediated by the innate and adaptive immune system, such as responses to infectious diseases and chronic inflammatory disorders. In conclusion, immune cells are an important target of vitamin D and common genes may serve as biomarkers for personal responses to the micronutrient.

scholarly journals Key Vitamin D Target Genes with Functions in the Immune System

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1140 ◽  
Author(s):  
Oona Koivisto ◽  
Andrea Hanel ◽  
Carsten Carlberg
Keyword(s):  
Vitamin D ◽  
Adaptive Immunity ◽  
Vitamin D3 ◽  
Target Genes ◽  
Mononuclear Cells ◽  
Active Form ◽  
Biologically Active ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Innate And Adaptive Immunity

The biologically active form of vitamin D3, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), modulates innate and adaptive immunity via genes regulated by the transcription factor vitamin D receptor (VDR). In order to identify the key vitamin D target genes involved in these processes, transcriptome-wide datasets were compared, which were obtained from a human monocytic cell line (THP-1) and peripheral blood mononuclear cells (PBMCs) treated in vitro by 1,25(OH)2D3, filtered using different approaches, as well as from PBMCs of individuals supplemented with a vitamin D3 bolus. The led to the genes ACVRL1, CAMP, CD14, CD93, CEBPB, FN1, MAPK13, NINJ1, LILRB4, LRRC25, SEMA6B, SRGN, THBD, THEMIS2 and TREM1. Public epigenome- and transcriptome-wide data from THP-1 cells were used to characterize these genes based on the level of their VDR-driven enhancers as well as the level of the dynamics of their mRNA production. Both types of datasets allowed the categorization of the vitamin D target genes into three groups according to their role in (i) acute response to infection, (ii) infection in general and (iii) autoimmunity. In conclusion, 15 genes were identified as major mediators of the action of vitamin D in innate and adaptive immunity and their individual functions are explained based on different gene regulatory scenarios.

scholarly journals Selective Biological Effects of Selenium-Enriched Polysaccharide (Se-Le-30) Isolated from Lentinula edodes Mycelium on Human Immune Cells

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1777
Author(s):  
Beata Kaleta ◽  
Aleksander Roszczyk ◽  
Michał Zych ◽  
Monika Kniotek ◽  
Radosław Zagożdżon ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Lentinula Edodes ◽  
Human Peripheral Blood ◽  
Biological Effects ◽  
Edible Mushroom ◽  
Biologically Active ◽  
Peripheral Blood Mononuclear ◽  
Tnf Α ◽  
Human Immune ◽  
Necrosis Factor

A common edible mushroom Lentinula edodes, is an important source of numerous biologically active substances, including polysaccharides, with immunomodulatory and antitumor properties. In the present work, the biological activity of the crude, homogenous (Se)-enriched fraction (named Se-Le-30), which has been isolated from L. edodes mycelium by a modified Chihara method towards human peripheral blood mononuclear cells (PBMCs) and peripheral granulocytes, was investigated. The Se-Le-30 fraction, an analog of lentinan, significantly inhibited the proliferation of human PBMCs stimulated with anti-CD3 antibodies or allostimulated, and down-regulated the production of tumor necrosis factor (TNF)-α by CD3+ T cells. Moreover, it was found that Se-Le-30 significantly reduced the cytotoxic activity of human natural killer (NK) cells. The results suggested the selective immunosuppressive activity of this fraction, which is non-typical for mushroom derived polysaccharides.

scholarly journals MYO1F regulates antifungal immunity by regulating acetylation of microtubules

2021 ◽  
Vol 118 (30) ◽  
pp. e2100230118
Author(s):  
Wanwei Sun ◽  
Xiaojian Ma ◽  
Heping Wang ◽  
Yanyun Du ◽  
Jianwen Chen ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Mononuclear Cells ◽  
Fungal Infections ◽  
Human Peripheral Blood ◽  
Systemic Infection ◽  
Mouse Bone Marrow ◽  
Peripheral Blood Mononuclear ◽  
Expression Of Genes ◽  
Proinflammatory Responses ◽  
Antifungal Immunity

Opportunistic fungal infections have become one of the leading causes of death among immunocompromised patients, resulting in an estimated 1.5 million deaths each year worldwide. The molecular mechanisms that promote host defense against fungal infections remain elusive. Here, we find that Myosin IF (MYO1F), an unconventional myosin, promotes the expression of genes that are critical for antifungal innate immune signaling and proinflammatory responses. Mechanistically, MYO1F is required for dectin-induced α-tubulin acetylation, acting as an adaptor that recruits both the adaptor AP2A1 and α-tubulin N-acetyltransferase 1 to α-tubulin; in turn, these events control the membrane-to-cytoplasm trafficking of spleen tyrosine kinase and caspase recruitment domain-containing protein 9. Myo1f-deficient mice are more susceptible than their wild-type counterparts to the lethal sequelae of systemic infection with Candida albicans. Notably, administration of Sirt2 deacetylase inhibitors, namely AGK2, AK-1, or AK-7, significantly increases the dectin-induced expression of proinflammatory genes in mouse bone marrow–derived macrophages and microglia, thereby protecting mice from both systemic and central nervous system C. albicans infections. AGK2 also promotes proinflammatory gene expression in human peripheral blood mononuclear cells after Dectin stimulation. Taken together, our findings describe a key role for MYO1F in promoting antifungal immunity by regulating the acetylation of α-tubulin and microtubules, and our findings suggest that Sirt2 deacetylase inhibitors may be developed as potential drugs for the treatment of fungal infections.

scholarly journals Transcriptome-Wide Profile of 25-Hydroxyvitamin D3 in Primary Immune Cells from Human Peripheral Blood

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 4100
Author(s):  
Andrea Hanel ◽  
Igor Bendik ◽  
Carsten Carlberg
Keyword(s):  
Vitamin D ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Human Peripheral Blood ◽  
Cell Types ◽  
Physiological Concentration ◽  
Peripheral Blood Mononuclear ◽  
Dihydroxyvitamin D3 ◽  
Interacting Protein

Vitamin D3 is an essential micronutrient mediating pleiotropic effects in multiple tissues and cell types via its metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), which activates the transcription factor vitamin D receptor. In this study, we used peripheral blood mononuclear cells (PBMCs) obtained from five healthy adults and investigated transcriptome-wide, whether the precursor of 1,25(OH)2D3, 25-hydroxyvitamin D3 (25(OH)D3), has gene regulatory potential on its own. Applying thresholds of >2 in fold change of gene expression and <0.05 as a false discovery rate, in this ex vivo approach the maximal physiological concentration of 25(OH)D3 (250 nM (nmol/L)) none of the study participants had a significant effect on their PBMC transcriptome. In contrast, 1000 and 10,000 nM 25(OH)D3 regulated 398 and 477 genes, respectively, which is comparable to the 625 genes responding to 10 nM 1,25(OH)2D3. The majority of these genes displayed specificity to the tested individuals, but not to the vitamin D metabolite. Interestingly, the genes MYLIP (myosin regulatory light chain interacting protein) and ABCG1 (ATP binding cassette subfamily G member 1) showed to be specific targets of 10,000 nM 25(OH)D3. In conclusion, 100- and 1000-fold higher 25(OH)D3 concentrations than the reference 10 nM 1,25(OH)2D3 are able to affect the transcriptome of PBMCs with a profile comparable to that of 1,25(OH)2D3.

scholarly journals Role of Paricalcitol in Modulating the Immune Response in Patients with Renal Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Silvia Lucisano ◽  
Adriana Arena ◽  
Giovanna Stassi ◽  
Daniela Iannello ◽  
Gaetano Montalto ◽  
...  
Keyword(s):  
Vitamin D ◽  
Inflammatory Markers ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
High Sensitivity ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
25 Oh Vitamin D

Introduction. The aim was to highlight the existence of a relationship between vitamin D deficiency, chronic inflammation, and proteinuria, by measuring neutrophil gelatinase associated lipocalin (NGAL) and common inflammatory markers after administration of paricalcitol, a vitamin D analog,in vivoandin vitro.Methods. 40 patients with end-stage chronic kidney disease (CKD) and secondary hyperparathyroidism and 40 healthy subjects were enrolled. Serum calcium, phosphorus, 25(OH)-vitamin D, parathyroid hormone (PTH), erythrocyte sedimentation rate, high-sensitivity C-reactive protein, interleukin- (IL-) 17, IL-6, IL-1β, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), plasmatic and urinary NGAL, and 24 h albuminuria and proteinuria were measured before and 24 h after an intravenous bolus of paricalcitol (5 mcg). Human peripheral blood mononuclear cells were isolated and stimulated with phytohaemagglutinin. NGAL, IL-1β, IL-17, IL-6, TNF-α, and IFN-γwere measured in the culture medium and in the 24 h urine collection.Results. 25(OH)-vitamin D was lower in CKD than in controls (p<0.0001), while inflammatory markers were higher in CKD group (p<0.0001).In vivoandin vitrostudies showed a downregulation of NGAL, IL-17, IL-6, IL-1β, TNF-α, and IFN-γafter paricalcitol administration (p<0.0001).Conclusions. 25(OH)-vitamin D regulates immune and inflammatory processes. Further studies are needed to confirm these data in order to improve the treatment of CKD patients.

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