The Role of Vitamin D in the Immune System as a Pro-survival Molecule

Chirumbolo, Salvatore; Bjørklund, Geir; Sboarina, Andrea; Vella, Antonio

doi:10.1016/j.clinthera.2017.03.021

Cited by 100 publications

(61 citation statements)

References 233 publications

(183 reference statements)

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“…Vitamin D is an ancient molecule that functions as both a nutrient and a hormone with metabolic and immunomodulatory properties; it regulates over 1,000 genes of the human genome (243,244). The vitamin D receptor (VDR) is a member of the nuclear receptor gene family and is expressed in virtually all nucleated cells.…”

Section: Vitamin Dmentioning

confidence: 99%

“…Genome-and transcriptome-wide studies indicate that vitamin D signaling modulates many inflammatory responses on several levels (245), including interference with NF-κB, via upregulation of IκB expression (246). In addition, the ability of vitamin D to inhibit metabolic stress and energy expenditure in a cell microenvironment suggests that this pleiotropic hormone has a broad task as a pro-survival agent (244).…”

Section: Vitamin Dmentioning

confidence: 99%

“…Of interest, Vitamin D has a high affinity binding for the GR (254), and was recently shown to increase, in a dosedependent manner, GR concentration in T cells (255). Based on its pleiotropic functions, vitamin D is considered a "master tuner" in shifting homeostatic balance from a pro-inflammatory to a pro-resolving status (244). Several studies demonstrated a dose-dependent response of vitamin D with respect to reducing inflammation, with 1 nM and 10 nM concentrations causing the greatest effects (248).…”

Section: Vitamin Dmentioning

confidence: 99%

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General Adaptation in Critical Illness: Glucocorticoid Receptor-alpha Master Regulator of Homeostatic Corrections

Meduri

Chrousos

2020

Front. Endocrinol.

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In critical illness, homeostatic corrections representing the culmination of hundreds of millions of years of evolution, are modulated by the activated glucocorticoid receptor alpha (GRα) and are associated with an enormous bioenergetic and metabolic cost. Appreciation of how homeostatic corrections work and how they evolved provides a conceptual framework to understand the complex pathobiology of critical illness. Emerging literature place the activated GRα at the center of all phases of disease development and resolution, including activation and re-enforcement of innate immunity, downregulation of pro-inflammatory transcription factors, and restoration of anatomy and function. By the time critically ill patients necessitate vital organ support for survival, they have reached near exhaustion or exhaustion of neuroendocrine homeostatic compensation, cell bio-energetic and adaptation functions, and reserves of vital micronutrients. We review how critical illness-related corticosteroid insufficiency, mitochondrial dysfunction/damage, and hypovitaminosis collectively interact to accelerate an anti-homeostatic active process of natural selection. Importantly, the allostatic overload imposed by these homeostatic corrections impacts negatively on both acute and long-term morbidity and mortality. Since the bioenergetic and metabolic reserves to support homeostatic corrections are time-limited, early interventions should be directed at increasing GRα and mitochondria number and function. Present understanding of the activated GC-GRα's role in immunomodulation and disease resolution should be taken into account when re-evaluating how to administer glucocorticoid treatment and co-interventions to improve cellular responsiveness. The activated GRα interdependence with functional mitochondria and three vitamin reserves (B1, C, and D) provides a rationale for co-interventions that include prolonged glucocorticoid treatment in association with rapid correction of hypovitaminosis.

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Section: Vitamin Dmentioning

confidence: 99%

Section: Vitamin Dmentioning

confidence: 99%

Section: Vitamin Dmentioning

confidence: 99%

See 1 more Smart Citation

General Adaptation in Critical Illness: Glucocorticoid Receptor-alpha Master Regulator of Homeostatic Corrections

Meduri

Chrousos

2020

Front. Endocrinol.

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“…Але, зважаючи на обмежений вибір лікарських засобів, які можна використовувати під час вагітності, дуже важливим є пошук нових методів профілактики та можливості прогнозування ризику реалізації перинатального інфікування. З огляду на це, цікавими є нові відомості про вплив вітаміну D (VD) на функціональний стан репродуктивної та імунної системи людини [4,5,6].Важливою ланкою у вивченні механізмів впливу кальцитріолу на організм людини є дані про наявність рецепторів вітаміну D(VDR) в багатьох органах і тканинах організму та інформація про поліморфізм генів, що кодують VDR [7,8].…”

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Calcitriol and polymorphism of the gene of the receptor vitamin D in the pathogenesis of perinatal infection (review)

Manasova¹,

Диденкул²,

Derishov³

et al. 2019

Neonatol. hìr. perinat. med.

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“…His Update focuses on the all-important role of vitamin D in immunity. [30][31][32][33][34][35] Richard I. Shader, MD Editor-in-Chief…”

mentioning

confidence: 99%

Vitamins C and D

Shader¹

2017

Clinical Therapeutics

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The Role of Vitamin D in the Immune System as a Pro-survival Molecule

Abstract: Vitamin D should be better highlighted in its molecular action and vitamin D receptor genomics to conceive a more suited therapeutic supplementation protocol in clinics.

Cited by 100 publications

References 233 publications

General Adaptation in Critical Illness: Glucocorticoid Receptor-alpha Master Regulator of Homeostatic Corrections

General Adaptation in Critical Illness: Glucocorticoid Receptor-alpha Master Regulator of Homeostatic Corrections

Calcitriol and polymorphism of the gene of the receptor vitamin D in the pathogenesis of perinatal infection (review)

Vitamins C and D

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