Expression of ß-defensins in intestines of chickens injected with vitamin D3 and lipopolysaccharide.

The objective of this study was to evaluate the effect of vitamin D3 (VD3) on the regulation of chicken intestinal ß-defensin genes under normal and lipopolysaccharides (LPS) conditions. Four treatment groups were used, including a negative control group, VD3-injection group, LPS-injection group, and both VD3-injection and LPS-injection group. At 4, 24, and 48 h post-injection, intestines were collected and RNA was isolated to measure the chicken ß-defensin genes with putative vitamin D responsive elements using quantitative polymerase chain reaction. Expressions of all 7 chicken ß-defensin genes was detectable in the intestines. Significant increases in GAL-6, -7 and -9 were found following LPS injection treatment at 4, 24, and 48 h post-injection, respectively, whereas VD3 injection did not affect the expression of any investigated genes under normal conditions. However, the expression of GAL-4, -5, -6, and -10 were synergistically upregulated by VD3 in combination with LPS. These results suggest that VD3 enhances the immune immunity during LPS challenge by inducing the expression of chicken ß-defensin genes when birds are exposed to immune stressors.

Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism.

Serotonin and vitamin D have been proposed to play a role in autism; however, no causal mechanism has been established. Here, we present evidence that vitamin D hormone (calcitriol) activates the transcription of the serotonin-synthesizing gene tryptophan hydroxylase 2 (TPH2) in the brain at a vitamin D response element (VDRE) and represses the transcription of TPH1 in tissues outside the blood-brain barrier at a distinct VDRE. The proposed mechanism explains 4 major characteristics associated with autism: the low concentrations of serotonin in the brain and its elevated concentrations in tissues outside the blood-brain barrier; the low concentrations of the vitamin D hormone precursor 25-hydroxyvitamin D [25(OH)D3]; the high male prevalence of autism; and the presence of maternal antibodies against fetal brain tissue. Two peptide hormones, oxytocin and vasopressin, are also associated with autism and genes encoding the oxytocin-neurophysin I preproprotein, the oxytocin receptor, and the arginine vasopressin receptor contain VDREs for activation. Supplementation with vitamin D and tryptophan is a practical and affordable solution to help prevent autism and possibly ameliorate some symptoms of the disorder.

Novel regulators of vitamin D action and metabolism: Lessons learned at the Los Angeles zoo.

We undertook an investigation of an outbreak of rachitic bone disease in the Emperor Tamarin New World primate colony at the Los Angeles Zoo in the mid-1980s. The disease phenotype resembled that observed in humans with an inactivating mutation of the vitamin D receptor (VDR), hypocalcemia, high 1,25-dihydroxyvitamin D (1,25-(OH)(2)D) levels, and rickets in rapidly growing adolescent primates. In contrast to the human disease, the New World primate VDR was functionally normal in all respects. The proximate cause of vitamin D hormone resistance in New World primates was determined to be the constitutive overexpression of a heterogeneous nuclear ribonucleoprotein in the A family which we coined the vitamin D response element binding protein (VDRE-BP). VDRE-BP competed in trans with the VDR-retinoid X receptor (RXR) for binding to the vitamin D response element. VDRE-BP-legislated resistance to 1,25-(OH)(2)D was antagonized (i.e., compensated) by another set of constitutively overexpressed proteins, the hsp-70-related intracellular vitamin D binding proteins (IDBPs). IDBPs, present but expressed at much lower levels in Old World primates including man, exhibited a high capacity for 25-hydroxylated vitamin D metabolites and functioned to traffic vitamin Ds to specific intracellular destinations to promote their action and metabolism.