Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 376
Filtrar
1.
Rev Endocr Metab Disord ; 24(2): 191-205, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36509987

RESUMO

Bone marrow contains resident cellular components that are not only involved in bone maintenance but also regulate hematopoiesis and immune responses. The immune system and bone interact with each other, coined osteoimmunology. Hashimoto's thyroiditis (HT) is one of the most common chronic autoimmune diseases which is accompanied by lymphocytic infiltration. It shows elevating thyroid autoantibody levels at an early stage and progresses to thyroid dysfunction ultimately. Different effects exert on bone metabolism during different phases of HT. In this review, we summarized the mechanisms of the long-term effects of HT on bone and the relationship between thyroid autoimmunity and osteoimmunology. For patients with HT, the bone is affected not only by thyroid function and the value of TSH, but also by the setting of the autoimmune background. The autoimmune background implies a breakdown of the mechanisms that control self-reactive system, featuring abnormal immune activation and presence of autoantibodies. The etiology of thyroid autoimmunity and osteoimmunology is complex and involves a number of immune cells, cytokines and chemokines, which regulate the pathogenesis of HT and osteoporosis at the same time, and have potential to affect each other. In addition, vitamin D works as a potent immunomodulator to influence both thyroid immunity and osteoimmunology. We conclude that HT affects bone metabolism at least through endocrine and immune pathways.


Assuntos
Osso e Ossos , Doença de Hashimoto , Doença de Hashimoto/imunologia , Doença de Hashimoto/metabolismo , Doença de Hashimoto/fisiopatologia , Osso e Ossos/imunologia , Osso e Ossos/metabolismo , Osso e Ossos/fisiopatologia , Humanos , Glândula Tireoide/imunologia , Glândula Tireoide/metabolismo , Glândula Tireoide/fisiopatologia , Hormônios Tireóideos/metabolismo , Osteoporose/metabolismo , Osteoporose/fisiopatologia , Vitamina D/imunologia , Vitamina D/metabolismo , Animais , Autoimunidade , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Doenças Autoimunes/fisiopatologia
2.
Int J Mol Sci ; 23(5)2022 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-35270015

RESUMO

Almost two years have passed since the outbreak reported for the first time in Wuhan of coronavirus disease 2019 (COVID-19), due to severe acute respiratory syndrome (SARS)-CoV-2 coronavirus, rapidly evolved into a pandemic. This infectious disease has stressed global health care systems. The mortality rate is higher, particularly in elderly population and in patients with comorbidities such as hypertension, diabetes mellitus, cardiovascular disease, chronic lung disease, chronic renal disease, and malignancy. Among them, subjects with diabetes have a high risk of developing severe form of COVID-19 and show increased mortality. How diabetes contributes to COVID-19 severity remains unclear. It has been hypothesized that it may be correlated with the effects of hyperglycemia on systemic inflammatory responses and immune system dysfunction. Vitamin D (VD) is a modulator of immune-response. Data from literature showed that vitamin D deficiency in COVID-19 patients increases COVID-19 severity, likely because of its negative impact on immune and inflammatory responses. Therefore, the use of vitamin D might play a role in some aspects of the infection, particularly the inflammatory state and the immune system function of patients. Moreover, a piece of evidence highlighted a link among vitamin D deficiency, obesity and diabetes, all factors associated with COVID-19 severity. Given this background, we performed an overview of the systematic reviews to assess the association between vitamin D supplementation and inflammatory markers in patients with diabetes; furthermore, vitamin D's possible role in COVID-19 patients was assessed as well. Three databases, namely MEDLINE, PubMed Central and the Cochrane Library of Systematic Reviews, were reviewed to retrieve the pertinent data. The aim of this review is to provide insight into the recent advances about the molecular basis of the relationship between vitamin D, immune response, inflammation, diabetes and COVID-19.


Assuntos
COVID-19/imunologia , Diabetes Mellitus/imunologia , Sistema Imunitário/imunologia , Inflamação/imunologia , Obesidade/imunologia , Vitamina D/imunologia , COVID-19/virologia , Humanos , Sistema Imunitário/efeitos dos fármacos , Metanálise como Assunto , SARS-CoV-2/fisiologia , Revisões Sistemáticas como Assunto , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Vitamina D/administração & dosagem , Vitaminas/administração & dosagem , Vitaminas/imunologia
3.
Nutrients ; 14(2)2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35057465

RESUMO

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 ß-defensin 2/defensin-ß4 (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.


Assuntos
Peptídeos Antimicrobianos/imunologia , Antivirais/imunologia , COVID-19/imunologia , Imunidade Inata/imunologia , SARS-CoV-2/imunologia , Vitamina D/análogos & derivados , Peptídeos Catiônicos Antimicrobianos/sangue , Peptídeos Catiônicos Antimicrobianos/imunologia , Peptídeos Antimicrobianos/sangue , Calcitriol/sangue , Calcitriol/imunologia , Catelicidinas/sangue , Catelicidinas/imunologia , Humanos , Receptores de Calcitriol/sangue , Receptores de Calcitriol/imunologia , Transdução de Sinais/imunologia , Vitamina D/sangue , Vitamina D/imunologia , Deficiência de Vitamina D/imunologia , Deficiência de Vitamina D/virologia , beta-Defensinas/sangue , beta-Defensinas/imunologia
4.
Expert Rev Anti Infect Ther ; 20(2): 231-241, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34112047

RESUMO

INTRODUCTION: Global emergence of coronavirus disease-19 (COVID-19) has clearly shown variable severity, mortality, and frequency between and within populations worldwide. These striking differences have made many biological variables attractive for future investigations. One of these variables, vitamin D, has been implicated in COVID-19 with rapidly growing scientific evidence. AREAS COVERED: The review intended to systematically explore the sources, and immunomodulatory role of vitamin D in COVID-19. Search engines and data sources including Google Scholar, PubMed, NCBI, Scopus, and Web of Science were used for data collection. The search terms used were Vitamin D, COVID-19, immune system, and antiviral mechanism. Overall, 232 sources of information were collected and 188 were included in this review. EXPERT OPINION: Interaction of vitamin D and vitamin D receptor (VDR) triggers the cellular events to modulate the immune system by regulation of many genes. Vitamin D operates as a double-edged sword against COVID-19. First, in macrophages, it promotes the production of antimicrobial and antiviral proteins like ß-defensin 2 and cathelicidin, and these proteins inhibit the replication of viral particles and promote the clearance of virus from the cells by autophagy. Second, it suppresses cytokine storm and inflammatory processes in COVID-19.


Assuntos
Fatores de Restrição Antivirais/imunologia , Autofagia , COVID-19 , Citocinas/imunologia , Vitamina D , COVID-19/complicações , COVID-19/imunologia , Humanos , Macrófagos/imunologia , Receptores de Calcitriol , SARS-CoV-2 , Vitamina D/imunologia , Vitaminas
5.
J Immunol Res ; 2021: 9782994, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34881335

RESUMO

BACKGROUND: Systemic sclerosis (SSc) is a chronic multisystem autoimmune condition defined by a complex pathobiology, comprising excessive fibrosis of skin and internal organs, peripheral vasculopathy with endothelial cell dysfunction, inadequate vascular repair and neovascularization, and aberrant immunity. Vitamin D is a steroid hormone with pleiotropic effects beyond its traditional role in calcium and bone homeostasis. Since vitamin D has immunomodulatory, cardioprotective, and antifibrotic properties, it could potentially interfere with SSc pathogenesis. Suboptimal vitamin D levels are classically recognized in scleroderma, irrespective of clinical and serological phenotype. AIM: This systematic review is aimed at investigating and clarifying the role of vitamin D in SSc and emphasizing the association of vitamin D status with different clinical settings. METHODS AND RESULTS: A systematic online search was performed, using PubMed databases to collect articles on the topic of vitamin D in SSc. The final analysis included 40 eligible articles. CONCLUSIONS: Hypovitaminosis D is common in SSc patients and could be associated with clinical and serologic patterns of the disease. Intervention for low serum vitamin D levels in SSc pathogenesis remains controversial, as well as the significance of vitamin D supplementation in such patients.


Assuntos
Escleroderma Sistêmico/imunologia , Deficiência de Vitamina D/imunologia , Vitamina D/imunologia , Suplementos Nutricionais , Humanos , Escleroderma Sistêmico/sangue , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/dietoterapia , Índice de Gravidade de Doença , Vitamina D/administração & dosagem , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico
6.
Life Sci ; 287: 120110, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34743945

RESUMO

For several years, scientists have recognized that vitamin D plays an important role in mineral and bone homeostasis. It was mostly used to treat osteoporosis and rickets in the past decades. Vitamin D has also been discovered to be modulator of the immune system and may play a role in a variety of diseases, including autoimmune diseases, in recent years. Vitamin D interaction with the vitamin D receptor (VDR), which has transcriptional imparts and is displayed on a variety of cell types, including those of the immune system, appears to be accountable for the immune-modulating effects. The action of tumor cells and vitamin D were the first to be investigated, but the spotlight is now on immunologic and purinergic systems. We conducted a systematic search in Pub Med as well as Google scholar for studies written in English. Vitamin D, cancer, purinergic signaling, and immune response were among the search words. Vitamin D has the potential to be a useful coadjuvant in cancer therapy and the purinergic system may be a potential treatment target to cancer therapy, according to our findings.


Assuntos
Antineoplásicos/uso terapêutico , Imunidade Celular/imunologia , Neoplasias/imunologia , Receptores de Calcitriol/imunologia , Receptores Purinérgicos/imunologia , Vitamina D/imunologia , Trifosfato de Adenosina/imunologia , Trifosfato de Adenosina/metabolismo , Antineoplásicos/farmacologia , Humanos , Imunidade Celular/efeitos dos fármacos , Fatores Imunológicos/imunologia , Fatores Imunológicos/metabolismo , Neoplasias/terapia , Receptores de Calcitriol/metabolismo , Receptores Purinérgicos/metabolismo , Vitamina D/farmacologia , Vitamina D/uso terapêutico
7.
PLoS Negl Trop Dis ; 15(10): e0009873, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34634046

RESUMO

A dysregulated or exacerbated inflammatory response is thought to be the key driver of the pathogenesis of severe disease caused by the mosquito-borne dengue virus (DENV). Compounds that restrict virus replication and modulate the inflammatory response could thus serve as promising therapeutics mitigating the disease pathogenesis. We and others have previously shown that macrophages, which are important cellular targets for DENV replication, differentiated in the presence of bioactive vitamin D (VitD3) are less permissive to viral replication, and produce lower levels of pro-inflammatory cytokines. Therefore, we here evaluated the extent and kinetics of innate immune responses of DENV-2 infected monocytes differentiated into macrophages in the presence (D3-MDMs) or absence of VitD3 (MDMs). We found that D3-MDMs expressed lower levels of RIG I, Toll-like receptor (TLR)3, and TLR7, as well as higher levels of SOCS-1 in response to DENV-2 infection. D3-MDMs produced lower levels of reactive oxygen species, related to a lower expression of TLR9. Moreover, although VitD3 treatment did not modulate either the expression of IFN-α or IFN-ß, higher expression of protein kinase R (PKR) and 2'-5'-oligoadenylate synthetase 1 (OAS1) mRNA were found in D3-MDMs. Importantly, the observed effects were independent of reduced infection, highlighting the intrinsic differences between D3-MDMs and MDMs. Taken together, our results suggest that differentiation of MDMs in the presence of VitD3 modulates innate immunity in responses to DENV-2 infection.


Assuntos
Diferenciação Celular , Vírus da Dengue/fisiologia , Dengue/imunologia , Macrófagos/citologia , Vitamina D/imunologia , 2',5'-Oligoadenilato Sintetase/genética , 2',5'-Oligoadenilato Sintetase/imunologia , Adulto , Animais , Dengue/genética , Dengue/fisiopatologia , Dengue/virologia , Vírus da Dengue/classificação , Vírus da Dengue/genética , Feminino , Humanos , Imunidade Inata , Interferon beta/genética , Interferon beta/imunologia , Macrófagos/imunologia , Masculino , Monócitos/citologia , Monócitos/imunologia , Replicação Viral , Adulto Jovem
8.
Nutrients ; 13(10)2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34684363

RESUMO

Food supplements (FS) are a concentrated source of vitamins, minerals, or other ingredients with nutritional or other physiological effects. Due to their easy availability, widespread advertising, and sometimes low price, increased consumption of this group of preparations has been observed. Therefore, the aim of the study was to assess the knowledge and intake of FS during the COVID-19 pandemic in Poland, with particular reference to FS containing zinc and vitamin D. It was noted that both of the above ingredients were used significantly more often by people with higher education (59.0%), with a medical background or related working in the medical field (54.5%), and/or exercising at home (60.1%). Preparations containing vitamin D were used by 22.8% of the respondents in the first wave, 37.6% in the second wave, and 32.9% in the third wave. To sum up, we showed the highest consumption of vitamin and mineral supplements, and preparations containing zinc and vitamin D were taken significantly more often by people with higher medical and related education. This indicates a high awareness of health aspects and the need for preventive measures in these groups.


Assuntos
COVID-19/imunologia , Suplementos Nutricionais/estatística & dados numéricos , Comportamentos Relacionados com a Saúde , Vitamina D/administração & dosagem , Zinco/administração & dosagem , Adulto , Feminino , Humanos , Masculino , Polônia , SARS-CoV-2 , Oligoelementos/administração & dosagem , Oligoelementos/imunologia , Vitamina D/imunologia , Vitaminas/administração & dosagem , Vitaminas/imunologia , Zinco/imunologia
9.
Int J Mol Sci ; 22(16)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34445700

RESUMO

Severe acute respiratory syndrome coronavirus 2 is a new, highly pathogenic virus that has recently elicited a global pandemic called the 2019 coronavirus disease (COVID-19). COVID-19 is characterized by significant immune dysfunction, which is caused by strong but unregulated innate immunity with depressed adaptive immunity. Reduced and delayed responses to interferons (IFN-I/IFN-III) can increase the synthesis of proinflammatory cytokines and extensive immune cell infiltration into the airways, leading to pulmonary disease. The development of effective treatments for severe COVID-19 patients relies on our knowledge of the pathophysiological components of this imbalanced innate immune response. Strategies to address innate response factors will be essential. Significant efforts are currently underway to develop vaccines against SARS-CoV-2. COVID-19 vaccines, such as inactivated DNA, mRNA, and protein subunit vaccines, have already been applied in clinical use. Various vaccines display different levels of effectiveness, and it is important to continue to optimize and update their composition in order to increase their effectiveness. However, due to the continuous emergence of variant viruses, improving the immunity of the general public may also increase the effectiveness of the vaccines. Many observational studies have demonstrated that serum levels of vitamin D are inversely correlated with the incidence or severity of COVID-19. Extensive evidence has shown that vitamin D supplementation could be vital in mitigating the progression of COVID-19 to reduce its severity. Vitamin D defends against SARS-CoV-2 through a complex mechanism through interactions between the modulation of innate and adaptive immune reactions, ACE2 expression, and inhibition of the renin-angiotensin system (RAS). However, it remains unclear whether Vit-D also plays an important role in the effectiveness of different COVID-19 vaccines. Based on analysis of the molecular mechanism involved, we speculated that vit-D, via various immune signaling pathways, plays a complementary role in the development of vaccine efficacy.


Assuntos
Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , Vitamina D/administração & dosagem , Vitamina D/sangue , Animais , COVID-19/sangue , COVID-19/imunologia , Vacinas contra COVID-19/imunologia , Ensaios Clínicos como Assunto , Humanos , Imunogenicidade da Vacina , Pandemias/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2/isolamento & purificação , Vitamina D/imunologia
10.
Mol Cell Biochem ; 476(12): 4351-4362, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34453644

RESUMO

Vitamin D is an immunomodulatory hormone with an established role in calcium and phosphate metabolism and skeletal mineralization. Evidence showing its immunological benefits by regulating essential components of the innate and adaptive immune system is prevalent. Vitamin D deficiency is reported worldwide and is thereby found to be associated with various immune-related diseases. Rheumatoid Arthritis and COVID-19 are two such diseases, sharing a similar hyperinflammatory response. Various studies have found an association of lower Vitamin D levels to be associated with both these diseases. However, contrasting data is also reported. We review here the available scientific data on risk factor association and supplementation benefits of Vitamin D in Rheumatoid Arthritis and COVID-19, intending to critically evaluate the literature.


Assuntos
Artrite Reumatoide/dietoterapia , COVID-19/etiologia , Deficiência de Vitamina D/complicações , Vitamina D/fisiologia , Artrite Reumatoide/etiologia , Humanos , Fatores de Risco , Vitamina D/imunologia , Vitamina D/uso terapêutico , Deficiência de Vitamina D/dietoterapia
11.
J Steroid Biochem Mol Biol ; 213: 105957, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34329737

RESUMO

This review examines the beneficial effects of ultraviolet radiation on systemic autoimmune diseases, including multiple sclerosis and type I diabetes, where the epidemiological evidence for the vitamin D-independent effects of sunlight is most apparent. Ultraviolet radiation, in addition to its role in the synthesis of vitamin D, stimulates anti-inflammatory pathways, alters the composition of dendritic cells, T cells, and T regulatory cells, and induces nitric oxide synthase and heme oxygenase metabolic pathways, which may directly or indirectly mitigate disease progression and susceptibility. Recent work has also explored how the immune-modulating functions of ultraviolet radiation affect type II diabetes, cancer, and the current global pandemic caused by SARS-CoV-2. These diseases are particularly important amidst global changes in lifestyle that result in unhealthy eating, increased sedentary habits, and alcohol and tobacco consumption. Compelling epidemiological data shows increased ultraviolet radiation associated with reduced rates of certain cancers, such as colorectal cancer, breast cancer, non-Hodgkins lymphoma, and ultraviolet radiation exposure correlated with susceptibility and mortality rates of COVID-19. Therefore, understanding the effects of ultraviolet radiation on both vitamin D-dependent and -independent pathways is necessary to understand how they influence the course of many human diseases.


Assuntos
COVID-19/prevenção & controle , Diabetes Mellitus Tipo 1/prevenção & controle , Diabetes Mellitus Tipo 2/prevenção & controle , Esclerose Múltipla/prevenção & controle , Neoplasias/prevenção & controle , Luz Solar , Vitamina D/metabolismo , Consumo de Bebidas Alcoólicas/efeitos adversos , COVID-19/imunologia , COVID-19/patologia , COVID-19/virologia , Células Dendríticas/imunologia , Células Dendríticas/efeitos da radiação , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/patologia , Progressão da Doença , Suscetibilidade a Doenças , Heme Oxigenase (Desciclizante)/genética , Heme Oxigenase (Desciclizante)/imunologia , Humanos , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Neoplasias/imunologia , Neoplasias/patologia , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase/imunologia , SARS-CoV-2/patogenicidade , SARS-CoV-2/efeitos da radiação , Comportamento Sedentário , Linfócitos T/imunologia , Linfócitos T/efeitos da radiação , Vitamina D/imunologia
12.
Nutrients ; 13(6)2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34064075

RESUMO

Celiac disease (CD) and autoimmune thyroid diseases (AITD) like Hashimoto's thyroiditis (HT) and Graves' disease (GD) frequently coexist, entailing numerous potential impacts on diagnostic and therapeutic approaches. Possible correlations might exist through gut microbiota, regulating the immune system and inflammatory responses, promoting autoimmune diseases, as well as shared cytokines in pathogenesis pathways, cross-reacting antibodies or malabsorption of micronutrients that are essential for the thyroid like iron or vitamin D. Vitamin D deficiency is a common finding in patients with AITD, but might protect from autoimmunity by wielding immunoregulatory and tolerogenic impacts. Additionally, vitamin D is assumed to be involved in the onset and progression of CD, presumably plays a substantial protective role for intestinal mucosa and affects the thyroid via its immunomodulatory effects. Iron is an essential micronutrient for the thyroid gland needed for effective iodine utilization by the iron-dependent enzyme thyroid iodine peroxidase (TPO). Despite being crucial for thyroid hormone synthesis, iron deficiency (ID) is a common finding in patients with hypothyroidism like HT and is frequently found in patients with CD. A literature research was conducted to examine the interplay between CD, AITD, vitamin D and iron deficiency. This narrative review highlights the relevant correlation of the two disease entities CD and AITD, their reciprocal impact and possible therapeutic options that should be further explored by future studies.


Assuntos
Doença Celíaca/imunologia , Ferro/imunologia , Glândula Tireoide/imunologia , Tireoidite Autoimune/imunologia , Vitamina D/imunologia , Autoimunidade/imunologia , Doença Celíaca/sangue , Microbioma Gastrointestinal/imunologia , Humanos , Ferro/sangue , Deficiências de Ferro , Tireoidite Autoimune/sangue , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/imunologia
13.
Int J Mol Sci ; 22(9)2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-34068701

RESUMO

In addition to its canonical functions, vitamin D has been proposed to be an important mediator of the immune system. Despite ample sunshine, vitamin D deficiency is prevalent (>80%) in the Middle East, resulting in a high rate of supplementation. However, the underlying molecular mechanisms of the specific regimen prescribed and the potential factors affecting an individual's response to vitamin D supplementation are not well characterized. Our objective is to describe the changes in the blood transcriptome and explore the potential mechanisms associated with vitamin D3 supplementation in one hundred vitamin D-deficient women who were given a weekly oral dose (50,000 IU) of vitamin D3 for three months. A high-throughput targeted PCR, composed of 264 genes representing the important blood transcriptomic fingerprints of health and disease states, was performed on pre and post-supplementation blood samples to profile the molecular response to vitamin D3. We identified 54 differentially expressed genes that were strongly modulated by vitamin D3 supplementation. Network analyses showed significant changes in the immune-related pathways such as TLR4/CD14 and IFN receptors, and catabolic processes related to NF-kB, which were subsequently confirmed by gene ontology enrichment analyses. We proposed a model for vitamin D3 response based on the expression changes of molecules involved in the receptor-mediated intra-cellular signaling pathways and the ensuing predicted effects on cytokine production. Overall, vitamin D3 has a strong effect on the immune system, G-coupled protein receptor signaling, and the ubiquitin system. We highlighted the major molecular changes and biological processes induced by vitamin D3, which will help to further investigate the effectiveness of vitamin D3 supplementation among individuals in the Middle East as well as other regions.


Assuntos
Colecalciferol/genética , Imunomodulação/imunologia , Receptores de Lipopolissacarídeos/genética , Receptor 4 Toll-Like/genética , Vitamina D/genética , Adolescente , Adulto , Colecalciferol/administração & dosagem , Colecalciferol/imunologia , Suplementos Nutricionais , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Imunomodulação/efeitos dos fármacos , Terapia Nutricional , Vitamina D/imunologia , Deficiência de Vitamina D/dietoterapia , Deficiência de Vitamina D/genética , Deficiência de Vitamina D/imunologia , Deficiência de Vitamina D/patologia , Adulto Jovem
14.
Front Immunol ; 12: 643298, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34025655

RESUMO

The immune system plays a key role in the protective response against oral cancer; however, the tumor microenvironment (TME) impairs this anti-cancer response by modulating T helper (Th) responses and promoting an anti-inflammatory environment. Regulatory T cells (Tregs) and Th2 effector cells (Teff) are associated with poor prognosis in oral squamous cell carcinoma (OSCC). However, the main immunomodulatory mechanisms associated with the enrichment of these subsets in OSCC remain unknown. We characterized Th-like lineages in Tregs and Teff and evaluated immunomodulatory changes induced by the TME in OSCC. Our phenotypic data revealed a higher distribution of tumour-infiltrating CCR8+ and Th2-like Treg in OSCC compared with non-malignant samples, whereas the percentages of Th1 cells were reduced in cancer. We then analyzed the direct effect of the TME by exposing T cell subsets to cancer secretomes and observed the OSCC secretome induced CCR8 expression and reduced cytokine production from both subsets. Transcriptomic analysis showed that the co-culture with OSCC secretome induced several gene changes associated with the vitamin D (VitD) signaling pathway in T cells. In addition, proteomic analysis identified the presence of several proteins associated with prostaglandin E2 (PGE2) production by rapid membrane VitD signaling and a reduced presence of the VitD binding protein. Thus, we analyzed the effect of VitD and PGE2 and observed that VitD promotes a regulatory Th2-like response with CCR8 expression whilst PGE2 also modulated CCR8 but inhibited cytokine production in combination with VitD. Finally, we evaluated the presence of CCR8 ligand in OSCC and observed increased chemokine CCL18, which was also able to upregulate CCR8 in activated Th cells. Overall, our data showed the immunomodulatory changes induced by the TME involving CCR8 expression and regulatory Th2 phenotypes, which are associated with PGE2 mediated VitD signaling pathway and CCL18 expression in OSCC.


Assuntos
Regulação Neoplásica da Expressão Gênica/imunologia , Imunomodulação , Neoplasias Bucais/imunologia , Proteínas de Neoplasias/imunologia , Receptores CCR8/imunologia , Transdução de Sinais/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Linfócitos T Reguladores/imunologia , Células Th2/imunologia , Microambiente Tumoral/imunologia , Vitamina D/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Linfócitos T Reguladores/patologia , Células Th2/patologia
16.
Immunotherapy ; 13(9): 753-765, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33906375

RESUMO

A dysregulated immune response characterized by the hyperproduction of several pro-inflammatory cytokines (a.k.a. 'cytokine storm') plays a central role in the pathophysiology of severe coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this Perspective article we discuss the evidence for synergistic anti-inflammatory and immunomodulatory properties exerted by vitamin D and dipeptidyl peptidase-4 (DPP-4) inhibitors, the latter being a class of antihyperglycemic agents used for the treatment of Type 2 diabetes, which have also been reported as immunomodulators. Then, we provide the rationale for investigation of vitamin D and DPP-4 inhibitor combination therapy (VIDPP-4i) as an immunomodulation strategy to ratchet down the virulence of SARS-CoV-2, prevent disease progression and modulate the cytokine storm in COVID-19.


Lay abstract The so-called 'cytokine storm' that drives the hyperproduction of pro-inflammatory mediators, plays a central role in the pathophysiology of severe coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Vitamin D has increasingly been shown to play anti-inflammatory and immunomodulatory properties beyond its role in the regulation of bone homeostasis. Similarly, dipeptidyl peptidase-4 inhibitors (DPP-4i) ­ a class of antihyperglycemic agents used for the treatment of Type 2 diabetes ­ have been reported as immunomodulators regardless of their glucose-lowering properties. We, therefore, discuss the role of vitamin D and DPP-4 inhibitor combination therapy (VIDPP-4i) as a potential immunomodulation strategy to prevent the development and/or halt the progression of the COVID-19-induced cytokine storm, particularly in patients with diabetes and cardiovascular disease.


Assuntos
COVID-19/terapia , Síndrome da Liberação de Citocina/prevenção & controle , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Imunoterapia/métodos , SARS-CoV-2/imunologia , Vitamina D/uso terapêutico , COVID-19/imunologia , COVID-19/virologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/metabolismo , Citocinas/imunologia , Citocinas/metabolismo , Inibidores da Dipeptidil Peptidase IV/imunologia , Quimioterapia Combinada , Humanos , Avaliação de Resultados em Cuidados de Saúde , SARS-CoV-2/fisiologia , Vitamina D/imunologia
17.
Int Immunopharmacol ; 97: 107686, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33930705

RESUMO

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is having a disastrous impact on global health. Recently, several studies examined the potential of vitamin D to reduce the effects of SARS-CoV-2 infection by modulating the immune system. Indeed, vitamin D has been found to boost the innate immune system and stimulate the adaptive immune response against SARS-CoV-2 infection. In this review, we provide a comprehensive update of the immunological mechanisms underlying the positive effects of vitamin D in reducing SARS-CoV-2 infection as well as a thorough survey of the recent epidemiological studies and clinical trials that tested vitamin D as a potential therapeutic agent against COVID-19 infection. We believe that a better understanding of the histopathology and immunopathology of the disease as well as the mechanism of vitamin D effects on COVID-19 severity will ultimately pave the way for a more effective prevention and control of this global pandemic.


Assuntos
COVID-19/prevenção & controle , Vitamina D/farmacologia , Vitamina D/uso terapêutico , Imunidade Adaptativa/efeitos dos fármacos , COVID-19/etiologia , COVID-19/imunologia , Suplementos Nutricionais , Humanos , Imunidade Inata/efeitos dos fármacos , Estações do Ano , Índice de Gravidade de Doença , Vitamina D/imunologia , Vitamina D/metabolismo
18.
J Endocrinol Invest ; 44(12): 2601-2607, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33818731

RESUMO

PURPOSE: The aim of the study was to investigate the association between serum 25-hydroxyvitamin D status within the last 6 months prior to COVID-19 infection and parameters of immune function and clinical outcomes. METHODS: Fifty-six patients, who were admitted to the emergency clinic and diagnosed with COVID-19 infection, were included in the study. Data on clinical characteristics, inflammatory parameters and vitamin D status were recorded for each patient. All the participants had data on 25-hydroxyvitamin D status within the last 6 months prior to COVID-19 infection. RESULTS: The patients were stratified as those with vitamin D status less than 20 ng/mL and higher than 20 ng/mL. A group with vitamin D status less than 20 ng/mL had lower lymphocyte counts and lower haemoglobin levels that was statistically significant (respectively; p = 0.021, p = 0.035). Higher C-reactive protein (CRP) levels were seen in the vitamin D-deficient group (p = 0.013). It was observed that vitamin D status of the patients who required oxygen therapy were lower than those who did not require oxygen therapy, not statistically significant (p = 0.05). Patients who did not use vitamin D supplementation within 6 months prior to COVID-19 infection had more likely to be diagnosed with pneumonia (p = 0.004). CONCLUSION: Cases with lower vitamin D status had increased inflammatory markers and worse clinical outcomes than patients with higher vitamin D status. This study suggests that vitamin D status can be used as a prognostic factor in COVID-19 patients, and vitamin D supplementation can be recommended to improve the clinical outcomes in COVID-19 infection.


Assuntos
COVID-19/sangue , Estado Nutricional , Deficiência de Vitamina D/sangue , Vitamina D/análogos & derivados , Vitamina D/sangue , Adulto , Idoso , Proteína C-Reativa/análise , COVID-19/complicações , COVID-19/imunologia , Comorbidade , Suplementos Nutricionais , Feminino , Hemoglobinas/metabolismo , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Oxigenoterapia , Pneumonia/complicações , Pneumonia/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento , Vitamina D/imunologia , Vitamina D/uso terapêutico , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/imunologia
19.
Rev Esp Geriatr Gerontol ; 56(3): 177-182, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33642133

RESUMO

The coronavirus disease 2019 (COVID-19) produces severe respiratory symptoms such as bilateral pneumonia associated to a high morbidity and mortality, especially in patients of advanced age. Vitamin D deficiency has been reported in several chronic conditions associated with increased inflammation and dysregulation of the immune system. Vitamin D in modulates immune function too. Vitamin D receptor (VDR) is expressed by most immune cells, including B and T lymphocytes, monocytes, macrophages, and dendritic cells and the signalling of vitamin D and VDR together has an anti-inflammatory effect. Some studies have reported that vitamin D treatment could be useful for the prevention and treatment of COVID-19 because vitamin D plays an important role as a modulator of immunocompetence. Over the last few months, some studies have hypothesized the possible beneficial effect of vitamin D supplementation in patients with COVID-19 in order to improve the immune balance and prevent the hyperinflammatory cytokine storm. Some preliminary studies have already shown promising results with vitamin D supplementation in hospitalized COVID-19 patients. Vitamin D should be administered daily until adequate levels are achieved due to vitamin D behaves as a negative acute phase reactant (APR). Despite the lack of evidence on specific doses of vitamin D to treat COVID-19 in older adults, authors consider it is necessary to standardize the use in clinical practice. These recommendations advice supplement vitamin D in a protocoled fashion based on expert opinions, level of evidence 5.


Assuntos
COVID-19/terapia , Síndrome da Liberação de Citocina , Suplementos Nutricionais , Geriatria , Deficiência de Vitamina D/terapia , Vitamina D/administração & dosagem , Vitaminas/administração & dosagem , Idoso , COVID-19/complicações , COVID-19/imunologia , COVID-19/prevenção & controle , Síndrome da Liberação de Citocina/prevenção & controle , Humanos , Receptores de Calcitriol/metabolismo , Sociedades Médicas , Espanha , Vitamina D/imunologia , Deficiência de Vitamina D/complicações , Vitaminas/imunologia
20.
J Infect Public Health ; 14(4): 444-445, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33751982

RESUMO

Responsive immunity plays an important role fighting against infections. Worldwide, Vitamin D deficiency is a major concern not only for musculoskeletal health but also affecting the immunity status in population. Amidst COVID-19 pandemic, it is imperative to establish the role of vitamin D in destruction of pathogens. Vitamin D awareness program at school level might be an effective health governance policy to educate populations for the importance of vitamin D in overall health.


Assuntos
COVID-19 , Sistema Imunitário , Vitamina D/imunologia , Humanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...