RESUMO
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.
Assuntos
Proteínas Aviárias/metabolismo , Colecalciferol/farmacologia , Expressão Gênica/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Lipopolissacarídeos/farmacologia , beta-Defensinas/metabolismo , Animais , Proteínas Aviárias/genética , Galinhas , Avaliação Pré-Clínica de Medicamentos , Intestinos/imunologia , Masculino , Regulação para Cima , Elemento de Resposta à Vitamina D/fisiologia , beta-Defensinas/genéticaRESUMO
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.
Assuntos
Transtorno Autístico/etiologia , Serotonina/biossíntese , Animais , Transtorno Autístico/sangue , Transtorno Autístico/dietoterapia , Transtorno Autístico/epidemiologia , Autoimunidade , População Negra , Barreira Hematoencefálica , Encéfalo/efeitos dos fármacos , Encéfalo/embriologia , Encéfalo/imunologia , Química Encefálica , Calcitriol , Anormalidades do Sistema Digestório/complicações , Doenças em Gêmeos , Estrogênios/fisiologia , Feminino , Feto/imunologia , Humanos , Incidência , Inflamação/induzido quimicamente , Masculino , Troca Materno-Fetal/imunologia , Modelos Biológicos , Mães , Ocitocina/sangue , Ocitocina/uso terapêutico , Gravidez , Receptores de Calcitriol/metabolismo , Serotonina/sangue , Triptofano Hidroxilase/biossíntese , Triptofano Hidroxilase/efeitos dos fármacos , Triptofano Hidroxilase/genética , Vitamina D/análogos & derivados , Vitamina D/sangue , Vitamina D/uso terapêutico , Deficiência de Vitamina D/epidemiologia , Elemento de Resposta à Vitamina D/fisiologiaAssuntos
Hormônio Paratireóideo , Cálcio/fisiologia , Humanos , Glândulas Paratireoides/metabolismo , Hormônio Paratireóideo/biossíntese , Hormônio Paratireóideo/química , Hormônio Paratireóideo/genética , Hormônio Paratireóideo/fisiologia , Fósforo/fisiologia , Receptores de Detecção de Cálcio/química , Receptores de Detecção de Cálcio/fisiologia , Vitamina D/análogos & derivados , Vitamina D/fisiologia , Elemento de Resposta à Vitamina D/fisiologiaRESUMO
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.