Two distinct but distantly related complementary DNAs encoding proteins sharing human interleukin-1 (IL-1) activity (termed IL-1 alpha and IL-1 beta), were isolated from a macrophage cDNA library. The primary translation products of the genes are 271 and 269 amino acids long, although expression in Escherichia coli of the carboxy-terminal 159 and 153 amino acids produces IL-1 biological activity.

Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs

The vitamin D endocrine system is essential for calcium and bone homeostasis. The precise mode of action and the full spectrum of activities of the vitamin D hormone, 1,25-dihydroxyvitamin D [1,25-(OH)2D], can now be better evaluated by critical analysis of mice with engineered deletion of the vitamin D receptor (VDR). Absence of a functional VDR or the key activating enzyme, 25-OHD-1α-hydroxylase (CYP27B1), in mice creates a bone and growth plate phenotype that mimics humans with the same congenital disease or severe vitamin D deficiency. The intestine is the key target for the VDR because high calcium intake, or selective VDR rescue in the intestine, restores a normal bone and growth plate phenotype.

The VDR is nearly ubiquitously expressed, and almost all cells respond to 1,25-(OH)2D exposure; about 3% of the mouse or human genome is regulated, directly and/or indirectly, by the vitamin D endocrine system, suggesting a more widespread function. VDR-deficient mice, but not vitamin D- or 1α-hydroxylase-deficient mice, and man develop total alopecia, indicating that the function of the VDR and its ligand is not fully overlapping. The immune system of VDR- or vitamin D-deficient mice is grossly normal but shows increased sensitivity to autoimmune diseases such as inflammatory bowel disease or type 1 diabetes after exposure to predisposing factors. VDR-deficient mice do not have a spontaneous increase in cancer but are more prone to oncogene- or chemocarcinogen-induced tumors. They also develop high renin hypertension, cardiac hypertrophy, and increased thrombogenicity. Vitamin D deficiency in humans is associated with increased prevalence of diseases, as predicted by the VDR null phenotype. Prospective vitamin D supplementation studies with multiple noncalcemic endpoints are needed to define the benefits of an optimal vitamin D status.

Vitamin D and Human Health: Lessons from Vitamin D Receptor Null Mice

IN THE DECADE SINCE THE VITAMIN D RECEPTOR (VDR) was cloned and recognized as a member of the superfamily of nuclear receptors that regulate gene expression in a ligand-dependent manner, the central role of VDR in the biology of vitamin D action has been illuminated and is being defined at the molecular level. Following renal production as the hormonal metabolite of vitamin D, 1a,25-dihydroxyvitamin D3 (1,25(OH)2D3) functions as the ligand for VDR, with the hormone–receptor complex inducing calcemic and phosphatemic effects that result in normal bone mineralization and remodeling. VDR not only mediates the action of 1,25(OH)2D3 in calcium/phosphate translocating tissues, primarily intestine, but also elicits a myriad of apparent bioactivities in other major cell systems in the organism, including immune, neural, epithelial, and endocrine. The scope of this review will be limited to highlighting the actions of 1,25(OH)2D3 mediated by nuclear VDR and discussing new developments in the structure/function analysis of the receptor, including the phenotype of VDR knockout mice and the biochemical classification of patients with point mutations in the receptor. These new advances, along with other recent research, will be interpreted to update our understanding of the molecular role of VDR, ranging from characterization of its natural gene and clinically significant polymorphisms, through its DNA contact sites and protein partners, to novel ligand analogs that hold the promise of influencing VDR conformation in a therapeutically beneficial fashion. VDR BIOLOGY

/pdf/the-nuclear-vitamin-d-receptor-biological-and-molecular-41a27f8wag.pdf

The nuclear vitamin D receptor: biological and molecular regulatory properties revealed.

https://www.easy-immune-health.com/support-files/distribution_of_vitamin_d_receptors_in_brain.pdf

Distribution of the Vitamin D receptor and 1α-hydroxylase in human brain

Expression and structure of the human NGF receptor

1,25-dihydroxyvitamin D3 regulates the synthesis of nerve growth factor in primary cultures of glial cells

A new gene in bacteriophage λ is described. The product of this gene cro prevents expression of immunity and regulates the expression of those genes to the left of the immunity region. cro- mutants have been isolated and characterized.

https://www.pnas.org/content/pnas/66/3/855.full.pdf

Regulation of Repressor Expression in λ

Glial cell line-derived neurotrophic factor (GDNF) has significant therapeutic potentials, in particular for neurodegenerative disorders. To determine factors that would enhance GDNF expression, we analysed the effect of 1,25-(OH)2 D3 in C6 glioma cells. Treatment of C6 cells with 10−7 M, 1,25-(OH)2 D3 for 48 h elicited an 18.5-fold increase in the level of GDNF mRNA. In addition, our results indicate that 1,25-(OH)2 D3 is effective at concentrations as low as 10−10 M and that retinoic acid has additive effects. These data indicate that 1,25-(OH)2 D3 is a potent inducer of GDNF expression and suggest that 1,25-(OH)2 D3 may contribute to the regulation of GDNF in vivo.

1,25-Dihydroxyvitamin D3, an inducer of glial cell line-derived neurotrophic factor.

Several new deletions of the λ prophage have been mapped, permitting the localization of sites in the λ genome for initiation of replication, for initiation of gene c I function and for the response to regulation by gene cro.

Isolation and characterization of deletions in bacteriophage lambda residing as prophage in E. coli K 12.

New amber (sus) mutants of bacteriophage λ have been isolated. Some of them were obtained by a new technique which yields preferentially N and R mutants. The sensitivity of these and other sus mutants towards various suppressors has been determined and is discussed. Conclusions are drawn about which λ functions are “catalytic” or “stoichiometric”.

Philippe Brachet

Papers

1,25-dihydroxyvitamin D3 regulates the synthesis of nerve growth factor in primary cultures of glial cells

Regulation of Repressor Expression in λ

1,25-Dihydroxyvitamin D3, an inducer of glial cell line-derived neurotrophic factor.

Isolation and characterization of deletions in bacteriophage lambda residing as prophage in E. coli K 12.

Isolation and characterization of new sus (amber) mutants of bacteriophage λ