scholarly journals Emerging Roles of Vitamin D-Induced Antimicrobial Peptides in Antiviral Innate Immunity

Nutrients ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 284
Author(s):  
John H. White
Keyword(s):  
Vitamin D ◽  
Innate Immunity ◽  
Antimicrobial Peptides ◽  
Active Form ◽  
Cytokine Network ◽  
Increased Risk ◽  
Tract Infections ◽  
Circulating Levels

Vitamin D deficiency, characterized by low circulating levels of calcifediol (25-hydroxyvitamin D, 25D) has been linked to increased risk of infections of bacterial and viral origin. Innate immune cells produce hormonal calcitriol (1,25-dihydroxyvitamin D, 1,25D) locally from circulating calcifediol in response to pathogen threat and an immune-specific cytokine network. Calcitriol regulates gene expression through its binding to the vitamin D receptor (VDR), a ligand-regulated transcription factor. The hormone-bound VDR induces the transcription of genes integral to innate immunity including pattern recognition receptors, cytokines, and most importantly antimicrobial peptides (AMPs). Transcription of the human AMP genes β-defensin 2/defensin-β4 (HBD2/DEFB4) and cathelicidin antimicrobial peptide (CAMP) is stimulated by the VDR bound to promoter-proximal vitamin D response elements. HDB2/DEFB4 and the active form of CAMP, the peptide LL-37, which form amphipathic secondary structures, were initially characterized for their antibacterial actively. Notably, calcitriol signaling induces secretion of antibacterial activity in vitro and in vivo, and low circulating levels of calcifediol are associated with diverse indications characterized by impaired antibacterial immunity such as dental caries and urinary tract infections. However, recent work has also provided evidence that the same AMPs are components of 1,25D-induced antiviral responses, including those against the etiological agent of the COVID-19 pandemic, the SARS-CoV2 coronavirus. This review surveys the evidence for 1,25D-induced antimicrobial activity in vitro and in vivo in humans and presents our current understanding of the potential mechanisms by which CAMP and HBD2/DEFB4 contribute to antiviral immunity.

scholarly journals Vitamin D Enhances Radiosensitivity of Colorectal Cancer by Reversing Epithelial-Mesenchymal Transition

2021 ◽  
Vol 9 ◽  
Author(s):  
Xinyue Yu ◽  
Qian Wang ◽  
Baocai Liu ◽  
Ning Zhang ◽  
Guanghui Cheng
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Epithelial Mesenchymal Transition ◽  
Active Form ◽  
Plasminogen Activator Inhibitor ◽  
Biologically Active ◽  
Plasminogen Activator Inhibitor 1 ◽  
Mesenchymal Transition

Colorectal cancer (CRC) is often resistant to conventional therapies. Previous studies have reported the anticancer effects of vitamin D in several cancers, its role in radiotherapy (RT) remains unknown. We found that 1α, 25-dihydroxyvitamin D3 (VD3), the biologically active form of vitamin D, had antitumor effect on CRC and sensitized CRC cells to ionizing radiation (IR). VD3 demonstrated synergistic effect in combination with IR, which were detected by colony formation and cell proliferation assay. Radiosensitivity restoration induced by VD3 was associated with a series of phenotypes, including apoptosis, autophagy, and epithelial-mesenchymal transition (EMT). Using proteomics, “regulation of cell migration” and “cadherin” were found to be obviously enriched GO terms. Moreover, cystatin D and plasminogen activator inhibitor-1 (PAI-1), the differentially expressed proteins, were associated with EMT. Next, we confirmed the contributions of these two genes in enhancing IR sensitivity of CRC cells upon inhibition of EMT. As determined by proteomics, the mechanism underlying such sensitivity involved partially block of JAK/STAT3 signaling pathway. Furthermore, VD3 also elicited sensitization to RT in xenograft CRC models without additional toxicity. Our study revealed that VD3 was able to act in synergy with IR both in vitro and in vivo and could also confer radiosensitivity by regulating EMT, thereby providing a novel insight for elevating the efficacy of therapeutic regimens.

scholarly journals β-Defensin 1 Contributes to Pulmonary Innate Immunity in Mice

2002 ◽  
Vol 70 (6) ◽  
pp. 3068-3072 ◽  
Author(s):  
Christian Moser ◽  
Daniel J. Weiner ◽  
Elena Lysenko ◽  
Robert Bals ◽  
Jeffrey N. Weiser ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Antimicrobial Peptides ◽  
Expression Profiles ◽  
Antibiotic Activity ◽  
In Vitro Assays ◽  
First Line ◽  
Initial Block ◽  
Direct Killing

ABSTRACT Innate immunity serves as a first line defense in vertebrate organisms by providing an initial barrier to microorganisms and triggering antigen-specific responses. Antimicrobial peptides are thought to be effectors of innate immunity through their antibiotic activity and direct killing of microorganisms. Evidence to support this hypothesis in vertebrates is indirect, based on expression profiles and in vitro assays using purified peptides. Here we investigated the function of antimicrobial peptides in vivo using mice deficient in an antimicrobial peptide, mouse β-defensin-1 (mBD-1). We find that loss of mBD-1 results in delayed clearance of Haemophilus influenzae from lung. These data demonstrate directly that antimicrobial peptides of vertebrates provide an initial block to bacteria at epithelial surfaces.

scholarly journals The role of vitamin D in breast cancer risk and progression

2021 ◽  
Author(s):  
Justine Vanhevel ◽  
Lieve Verlinden ◽  
Stefanie Doms ◽  
Hans Wildiers ◽  
Annemieke Verstuyf
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
Vitamin D3 ◽  
Epithelial Mesenchymal Transition ◽  
Active Form ◽  
Stem Cell Population ◽  
Mesenchymal Transition ◽  
Increased Risk ◽  
Vitamin D3 Supplementation

The active form of vitamin D3, 1,25-dihydroxvitamin D3 [1,25(OH)2D3], is primarily known as a key regulator of calcium and phosphate homeostasis. It exerts its biological functions by binding to the vitamin D receptor (VDR), a transcription factor that regulates gene expression in vitamin D-target tissues such as intestine, kidney and bone. Yet, the VDR is expressed in many additional normal and cancerous tissues, where it moderates the antiproliferative, prodifferentiating and immune-modulating effects of 1,25(OH)2D3. Interestingly, several epidemiological studies show that low levels of 25(OH)D3, a biological marker for 1,25(OH)2D3 status, are associated with increased risk of breast cancer (BC) development. Mendelian randomization studies, however, did not find any relationship between single-nucleotide polymorphisms in genes associated with lower serum 25(OH)D3 and BC risk. Nevertheless, multiple in vitro and in vivo preclinical studies illustrate that 1,25(OH)2D3 or its less calcaemic structural analogues influence diverse cellular processes in BC such as proliferation, differentiation, apoptosis, autophagy and the epithelial-mesenchymal transition. Recent insights also demonstrate that 1,25(OH)2D3 treatment impacts on cell metabolism and on the cancer stem cell population. The presence of VDR in the majority of BCs, together with the various antitumoural effects of 1,25(OH)2D3, have supported the evaluation of the effects of vitamin D3 supplementation on BC development. However, most randomized controlled clinical trials do not demonstrate a clear decrease of BC incidence with vitamin D3 supplementation. However, 1,25(OH)2D3 or its analogues seem biologically more active, and may have more potential anticancer activity in BC upon combination with existing cancer therapies.

scholarly journals Tight Junction Proteins Claudin-2 and -12 Are Critical for Vitamin D-dependent Ca2+ Absorption between Enterocytes

2008 ◽  
Vol 19 (5) ◽  
pp. 1912-1921 ◽  
Author(s):  
Hiroki Fujita ◽  
Kotaro Sugimoto ◽  
Shuichiro Inatomi ◽  
Toshihiro Maeda ◽  
Makoto Osanai ◽  
...  
Keyword(s):  
Vitamin D ◽  
Tight Junction ◽  
Active Form ◽  
Intestinal Epithelial ◽  
Tight Junction Proteins ◽  
Dihydroxyvitamin D ◽  
Intestinal Epithelia ◽  
Junction Proteins

Ca2+ is absorbed across intestinal epithelial monolayers via transcellular and paracellular pathways, and an active form of vitamin D3, 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], is known to promote intestinal Ca2+ absorption. However, the molecules driving the paracellular Ca2+ absorption and its vitamin D dependency remain obscure. Because the tight junction proteins claudins are suggested to form paracellular channels for selective ions between neighboring cells, we hypothesized that specific intestinal claudins might facilitate paracellular Ca2+ transport and that expression of these claudins could be induced by 1α,25(OH)2D3. Herein, we show, by using RNA interference and overexpression strategies, that claudin-2 and claudin-12 contribute to Ca2+ absorption in intestinal epithelial cells. We also provide evidence showing that expression of claudins-2 and -12 is up-regulated in enterocytes in vitro and in vivo by 1α,25(OH)2D3 through the vitamin D receptor. These findings strongly suggest that claudin-2- and/or claudin-12-based tight junctions form paracellular Ca2+ channels in intestinal epithelia, and they highlight a novel mechanism behind vitamin D-dependent calcium homeostasis.

scholarly journals Calcitriol Inhibits Hedgehog Signaling and Induces Vitamin D Receptor Signaling and Differentiation in thePatchedMouse Model of Embryonal Rhabdomyosarcoma

Sarcoma ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Anja Uhmann ◽  
Hannah Niemann ◽  
Bérénice Lammering ◽  
Cornelia Henkel ◽  
Ina Heß ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Hedgehog Signaling ◽  
Active Form ◽  
Embryonal Rhabdomyosarcoma ◽  
Late Response ◽  
Hh Signaling ◽  
Exogenous Supply

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Aberrant Hedgehog (Hh) signaling is characteristic of the embryonal subtype (ERMS) and of fusion-negative alveolar RMS. In the mouse, ERMS-like tumors can be induced by mutations in the Hh receptor Patched1 (Ptch). As in humans these tumors show increased Hh pathway activity. Here we demonstrate that the treatment with the active form of vitamin D3, calcitriol, inhibits Hh signaling and proliferation of murine ERMSin vivoandin vitro. Concomitantly, calcitriol activates vitamin D receptor (Vdr) signaling and induces tumor differentiation. In addition, calcitriol inhibits ERMS growth inPtch-mutant mice, which is, however, a rather late response. Taken together, our results suggest that exogenous supply of calcitriol could be beneficial in the treatment of RMS, especially in those which are associated with aberrant Hh signaling activity.

scholarly journals VDR Signaling via the Enzyme NAT2 Inhibits Colorectal Cancer Progression

2021 ◽  
Vol 12 ◽  
Author(s):  
Chaojun Zhu ◽  
Zihuan Wang ◽  
Jianqun Cai ◽  
Chunqiu Pan ◽  
Simin Lin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Cancer Progression ◽  
Active Form ◽  
Underlying Mechanism ◽  
Protective Effects ◽  
Lower Survival Rate ◽  
Migration Capacity

Recent epidemiological and preclinical evidence indicates that vitamin D3 inhibits colorectal cancer (CRC) progression, but the mechanism has not been completely elucidated. This study was designed to determine the protective effects of vitamin D3 and identify crucial targets and regulatory mechanisms in CRC. First, we confirmed that 1,25(OH)2D3, the active form of vitamin D3, suppressed the aggressive phenotype of CRC in vitro and in vivo. Based on a network pharmacological analysis, N-acetyltransferase 2 (NAT2) was identified as a potential target of vitamin D3 against CRC. Clinical data of CRC patients from our hospital and bioinformatics analysis by online databases indicated that NAT2 was downregulated in CRC specimens and that the lower expression of NAT2 was correlated with a higher metastasis risk and lower survival rate of CRC patients. Furthermore, we found that NAT2 suppressed the proliferation and migration capacity of CRC cells, and the JAK1/STAT3 signaling pathway might be the underlying mechanism. Moreover, Western blot and immunofluorescence staining assays demonstrated that 1,25(OH)2D3 promoted NAT2 expression, and the chromatin immunoprecipitation assay indicated that the vitamin D receptor (VDR) transcriptionally regulated NAT2. These findings expand the potential uses of vitamin D3 against CRC and introduce VDR signaling via the enzyme NAT2 as a potential diagnostic and therapeutic target for CRC.

scholarly journals Role of Vitamin D on the Inhibition of Gastrin Production After Cisplatin Treatment

2000 ◽  
Vol 7 (3) ◽  
pp. 115-119 ◽  
Author(s):  
Ying Wang ◽  
Surinder K. Aggarwal ◽  
Will Kopachik
Keyword(s):  
Vitamin D ◽  
Active Form ◽  
Treatment Groups ◽  
Calcium Supplements ◽  
Blot Technique ◽  
Before And After ◽  
Male Wistar Rats

In rats cisplatin induces hypocalcemia, bloating of the stomach, and ulceration ameliorated through calcium supplements. This study was undertaken to test the role of calcium on the gastrin mRNA production in vitro and in vivo. RIN B6 cells were cultured in medium with calcium (1.8, 3.6 and 7.2 mM) and the active form of vitamin D (calcijex). Cisplatin was added (10 μg/ml) for 12 hrs and cells were harvested for RNA from various treatment groups. Male Wistar rats were treated with cisplatin (9 mg/kg), before and after vitamin D (0.3 mg/100g/week). The rats were killed and stomach tissues excised on 1, 6, 10 and 15 days after cisplatin treatment. RNA from the stomach was analyzed using the northern blot technique. Gastrin mRNA was suppressed after cisplatin treatment both in vitro and in vivo. In vitro calcium but not vitamin D additions partially prevented the gastrin mRNA. In vivo, however, vitamin D and calcium were equally effective in preventing gastrin mRNA loss.

Akalzämische Vitamin-D-Analoga zeigen antifibrotische Effekte in vitro in hepatischen Sternzellen und in vivo im CCl4-Mausmodell

2019 ◽  
Author(s):  
FP Reiter ◽  
L Ye ◽  
F Bösch ◽  
R Wimmer ◽  
R Artmann ◽  
...  
Keyword(s):  
Vitamin D

Vitamin D as potential therapeutic anticancer agent

2018 ◽  
pp. 1-3
Keyword(s):  
Vitamin D ◽  
Anticancer Activity ◽  
Anticancer Agent ◽  
Antitumor Agents ◽  
Metastatic Potential ◽  
Anticancer Properties ◽  
Chemotherapy Agents

The role of vitamin D is implicated in carcinogenesis through numerous biological processes like induction of apoptosis, modulation of immune system inhibition of inflammation and cell proliferation and promotion of cell differentiation. Its use as additional adjuvant drug with cancer treatment may be novel combination for improved outcome of different cancers. Numerous preclinical, epidemiological and clinical studies support the role of vitamin D as an anticancer agent. Anticancer properties of vitamin D have been studied widely (both in vivo and in vitro) among various cancers and found to have promising results. There are considerable data that indicate synergistic potential of calcitriol and antitumor agents. Possible mechanisms for modulatory anticancer activity of vitamin D include its antiproliferative, prodifferentiating, and anti-angiogenic and apoptic properties. Calcitriol reduces invasiveness and metastatic potential of many cancer cells by inhibiting angiogenesis and regulating expression of the key molecules involved in invasion and metastasis. Anticancer activity of vitamin D is synergistic or additive with the antineoplastic actions of several drugs including cytotoxic chemotherapy agents like paclitaxel, docetaxel, platinum base compounds and mitoxantrone. Benefits of addition of vitamin D should be weighed against the risk of its toxicity.

Antimicrobial peptides for the treatment of pulmonary tuberculosis, allies or foes?

2018 ◽  
Vol 24 (10) ◽  
pp. 1138-1147
Author(s):  
Bruno Rivas-Santiago ◽  
Flor Torres-Juarez
Keyword(s):  
Pulmonary Tuberculosis ◽  
Antimicrobial Peptides ◽  
Experimental Models ◽  
New Drugs ◽  
World Health ◽  
Public Health Issue ◽  
Health Organization ◽  
Drug Resistant Strains

Tuberculosis is an ancient disease that has become a serious public health issue in recent years, although increasing incidence has been controlled, deaths caused by Mycobacterium tuberculosis have been accentuated due to the emerging of multi-drug resistant strains and the comorbidity with diabetes mellitus and HIV. This situation is threatening the goals of World Health Organization (WHO) to eradicate tuberculosis in 2035. WHO has called for the creation of new drugs as an alternative for the treatment of pulmonary tuberculosis, among the plausible molecules that can be used are the Antimicrobial Peptides (AMPs). These peptides have demonstrated remarkable efficacy to kill mycobacteria in vitro and in vivo in experimental models, nevertheless, these peptides not only have antimicrobial activity but also have a wide variety of functions such as angiogenesis, wound healing, immunomodulation and other well-described roles into the human physiology. Therapeutic strategies for tuberculosis using AMPs must be well thought prior to their clinical use; evaluating comorbidities, family history and risk factors to other diseases, since the wide function of AMPs, they could lead to collateral undesirable effects.

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