Stat1-Vitamin D Receptor Interactions Antagonize 1,25-Dihydroxyvitamin D Transcriptional Activity and Enhance Stat1-Mediated Transcription

Vidal, Marcos; Ramana, Chilakamarti V.; Dusso, Adriana

doi:10.1128/mcb.22.8.2777-2787.2002

Cited by 122 publications

(89 citation statements)

References 55 publications

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“…The VDR usually binds as a heterodimer with the retinoic X receptor (RXR), and the classical effects of 1,25(OH) 2 D 3 are the result of interactions with this nuclear receptor. With respect to its relevance in diabetes, the classical VDRE and other response sites are found within genes encoding proteins with important functions in beta cells and within genes encoding proteins with key roles throughout the immune system, such as cytokines and transcription factors [21][22][23][24]. [25][26][27].…”

Section: Molecular Action Of 1α25-dihydroxyvitamin Dmentioning

confidence: 99%

Vitamin D and diabetes

et al. 2005

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Vitamin D deficiency predisposes individuals to type 1 and type 2 diabetes, and receptors for its activated form-1α,25-dihydroxyvitamin D 3 -have been identified in both beta cells and immune cells. Vitamin D deficiency has been shown to impair insulin synthesis and secretion in humans and in animal models of diabetes, suggesting a role in the development of type 2 diabetes. Furthermore, epidemiological studies suggest a link between vitamin D deficiency in early life and the later onset of type 1 diabetes. In some populations, type 1 diabetes is associated with certain polymorphisms within the vitamin D receptor gene. In studies in nonobese diabetic mice, pharmacological doses of 1α,25-dihydroxyvitamin D 3 , or its structural analogues, have been shown to delay the onset of diabetes, mainly through immune modulation. Vitamin D deficiency may, therefore, be involved in the pathogenesis of both forms of diabetes, and a better understanding of the mechanisms involved could lead to the development of preventive strategies.

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Section: Molecular Action Of 1α25-dihydroxyvitamin Dmentioning

confidence: 99%

Vitamin D and diabetes

et al. 2005

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“…Undifferentiated monocytes are highly susceptible to 1,25(OH) 2 D 3 -mediated 24-hydroxylase induction, whereas differentiated or activated macrophages are resistant. The latter is due to an interplay between IFN-g-mediated and 1,25(OH) 2 D 3 -mediated effects: STAT-1, a transcription factor involved in IFN-g-signalling, interacts with the DNA-binding domain of the VDR, thereby prohibiting binding of the ligand-VDR-RXR complex to the 24-hydroxylase promoter and preventing 1,25(OH) 2 D 3 -mediated induction of the enzyme 46 . Remarkably, 24-hydroxylase expression in dendritic cells was only observed when the cells underwent their differentiation process in the presence of 1,25(OH) 2 D 3 45 .…”

Section: 25-dihydroxyvitamin D 3 and The Immune Systemmentioning

confidence: 99%

“…As it has been shown that up regulation of 1-a-hydroxylase and therefore 1,25(OH) 2 D 3 synthesis by APC occurs only at a later stage of macrophage activation, this system may act as a negative feedback loop in order to tone down inflammation 40 . Besides 1-a-hydroxylase, monocytes, macrophages and dendritic cells also express 24-hydroxylase 45,46 . The promoter of this gene comprises two VDRE, making 24-hydroxylase expression highly inducible by 1,25(OH) 2 D 3 47 .…”

Section: 25-dihydroxyvitamin D 3 and The Immune Systemmentioning

confidence: 99%

Vitamin D₃and the immune system: maintaining the balance in health and disease

et al. 2007

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“…A number of genetic variations are implicated as potentially disease-predisposing or disease-modifying factors. Germline polymorphisms of genes regulating Th1 immune responses, particularly those of major histocompatibility complex II (1, 2), IFN-g (3), IL-18 (4), and signal transducer and activator of transcription 1 (STAT1) (5,6), have been identified as potential disease susceptibility genes. However, little is known about the genetic regulation of granulomatous inflammation operating at the tissue level in patients with active pulmonary sarcoidosis.…”

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confidence: 99%