1α,25-Dihydroxy-3-epi-vitamin D3, a natural metabolite of 1α,25-dihydroxy vitamin D3: production and biological activity studies in pulmonary alveolar type II cells

Rehan, Virender K.; Torday, John S.; Peleg, Sara; Gennaro, Lynn A.; Vouros, Paul; Padbury, Jamés F.; Rao, Devara Sunita; Reddy, G. Satyanarayana

doi:10.1016/s1096-7192(02)00022-7

Cited by 121 publications

(89 citation statements)

References 23 publications

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“…The AHR results confirmed the histopathology scores, which showed few infiltrating inflammatory cells in the lungs of VDR KO mice primed to develop asthma. 1,25(OH) 2 D 3 has been hypothesized to be important in lung development, and VDR KO mice have been reported to have normal pulmonary function (20). However, AHR measurements have never previously been done on VDR KO mice.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D Receptor-Deficient Mice Fail to Develop Experimental Allergic Asthma

Wittke

Weaver²,

Mahon³

et al. 2004

The Journal of Immunology

186

132

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The active metabolite of vitamin D (1,25-dihydroxyvitamin D3 (1,25(OH)2D3)) is known to modulate the immune response in Th1 cell-directed diseases. To investigate the role of vitamin D in Th2 cell-directed diseases, experimental allergic asthma was induced in vitamin D receptor (VDR) knockout and in wild-type (WT) mice. As expected, WT mice developed symptoms of airway inflammation with an influx of eosinophils, elevated Th2 cytokine levels, mucous production, and airway hyperresponsiveness. The administration of 1,25(OH)2D3 had no effect on asthma severity. The only discernable effect of 1,25(OH)2D3 on experimental allergic asthma in WT mice was an increased expression of two Th2-related genes (soluble CD23 and GATA-3) in lungs of BALB/c mice exposed to Ag through the nasal route only. By contrast, asthma-induced VDR knockout mice failed to develop airway inflammation, eosinophilia, or airway hyperresponsiveness, despite high IgE concentrations and elevated Th2 cytokines. The data suggest that although 1,25(OH)2D3 induced these Th2-type genes, the treatment failed to have any affect on experimental asthma severity. However, VDR-deficient mice failed to develop experimental allergic asthma, suggesting an important role for the vitamin D endocrine system in the generation of Th2-driven inflammation in the lung.

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Section: Discussionmentioning

confidence: 99%

Vitamin D Receptor-Deficient Mice Fail to Develop Experimental Allergic Asthma

Wittke

Weaver²,

Mahon³

et al. 2004

The Journal of Immunology

186

132

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“…There was no significant effect of the hormone on SP-A mRNA and protein levels in cells incubated without Bt 2 cAMP, but the levels of expression of SP-A in these cells were very low, and further reduction in the expression levels may not have been readily detected. (48). NCI-H441 are derived from Clara cells of the lung rather than alveolar type II cells; they express SP-A and SP-B, but not SP-C, and do not contain the distinguishing feature of type II cells, lamellar bodies (19).…”

Section: 25(oh) 2 D 3 Generally Reduces Expression Of Sp-a In Hu-mentioning

confidence: 99%

“…Rat alveolar type II cells have been shown to contain the nuclear hormone receptor for 1,25(OH) 2 D 3 , which is responsible for many of its physiological effects (38). Recently, a report has suggested that a natural metabolite of 1,25(OH) 2 D 3 increases surfactant phospholipid and SP-B mRNA and protein synthesis in human NCI-H441 cells (48). Nevertheless, the effects of 1,25(OH) 2 D 3 on the expression of the various surfactant proteins in human fetal lung and epithelial cells have not been investigated.…”

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confidence: 99%

Regulation of human pulmonary surfactant protein gene expression by 1α,25-dihydroxyvitamin D₃

Phokela¹,

Peleg²,

Moya³

et al. 2005

American Journal of Physiology-Lung Cellular and Molecular Phys

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[1,25(OH)2D3] has been reported to stimulate lung maturity, alveolar type II cell differentiation, and pulmonary surfactant synthesis in rat lung. We hypothesized that 1,25(OH) 2D3 stimulates expression of surfactant protein-A (SP-A), SP-B, and SP-C in human fetal lung and type II cells. We found that immunoreactive vitamin D receptor was detectable in fetal lung tissue and type II cells only when incubated with 1,25(OH)2D3. 1,25(OH)2D3 significantly decreased SP-A mRNA in human fetal lung tissue but did not significantly decrease SP-A protein in the tissue. In type II cells, 1,25(OH)2D3 alone had no significant effect on SP-A mRNA or protein levels but reduced SP-A mRNA and protein in a dose-dependent manner when the cells were incubated with cAMP. SP-A mRNA levels in NCI-H441 cells, a nonciliated bronchiolar epithelial (Clara) cell line, were decreased in a dose-dependent manner in the absence or presence of cAMP. 1,25(OH)2D3 had no significant effect on SP-B mRNA levels in lung tissue but increased SP-B mRNA and protein levels in type II cells incubated in the absence or presence of cAMP. Expression of SP-C mRNA was unaffected by 1,25(OH)2D3 in lung tissue incubated Ϯ cAMP. These results suggest that regulation of surfactant protein gene expression in human lung and type II cells by 1,25(OH)2D3 is not coordinated; 1,25(OH)2D3 decreases SP-A mRNA and protein levels in both fetal lung tissue and type II cells, increases SP-B mRNA and protein levels only in type II cells, and has no effect on SP-C mRNA levels. alveolar type II cell; steroid hormone PULMONARY SURFACTANT IS a unique complex of phospholipids and proteins that maintains alveolar integrity by reducing surface tension at the alveolar air-liquid interface (15) and participates in host defense and the control of inflammation in the lung (16). Surfactant is composed of 90% lipids and 10% proteins by weight. Phosphatidylcholine, mostly dipalmitoyl phosphatidylcholine, constitutes 70 -80% of the lipid portion of surfactant. Several distinct lung-specific proteins make up the protein component of surfactant, surfactant protein-A (SP-A), SP-B, SP-C, and SP-D (23). Whereas the lipid portion of surfactant is largely responsible for its surface activity, the highly hydrophobic proteins SP-B and SP-C also play a direct role in influencing the surface tension-reducing properties of surfactant (54). On the other hand, SP-A and SP-D are hydrophilic members of the collectin family of proteins (25) that play important roles in the control of host defense and inflammation in the lung (16). Pulmonary alveolar type II epithelial cells that are positioned in the corners of the alveoli carry out the highly specialized functions of synthesizing, secreting, and reutilizing surfactant (36, 49). Surfactant synthesis is initiated in alveolar type II cells only after 75% of gestation is complete (43). Infants born before this period of gestation lack sufficient surfactant and are predisposed to develop respiratory distress syndrome, one of the leading causes of neonatal morbi...

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“…16 İnsan hücre kültürlerinden elde edilen veriler, vitamin D'nin insanlarda da sür-faktan sentezinde etkili olabileceğini desteklemektedir. 17 Dahası, insan akciğer fibroblastlarında da vitamin D reseptörlerinin gösterilmesi ve akciğer parankiminde yüksek düzeyde kalbindin-vitamin D bağımlı kalsiyum bağlayıcı protein-bulunması, vitamin D'nin akciğer kompliyansı üzerinde de etkili olduğunu düşündürmektedir. 18,19 Literatürde tek bir çalışmada YGT olan bebeklerde 25(OH)D 3 düzeyi sağlıklı kontrollere göre anlamlı olarak düşük bulunmuştur.…”

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Maternal Vitamin D Deficiency May be a Risk Factor for Transient Tachypnea of the Newborn

Gür¹,

Kasap²,

Genç³

et al. 2015

Turkiye Klinikleri J Gynecol Obst

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1α,25-Dihydroxy-3-epi-vitamin D3, a natural metabolite of 1α,25-dihydroxy vitamin D3: production and biological activity studies in pulmonary alveolar type II cells

Cited by 121 publications

References 23 publications

Vitamin D Receptor-Deficient Mice Fail to Develop Experimental Allergic Asthma

Vitamin D Receptor-Deficient Mice Fail to Develop Experimental Allergic Asthma

Regulation of human pulmonary surfactant protein gene expression by 1α,25-dihydroxyvitamin D₃

Maternal Vitamin D Deficiency May be a Risk Factor for Transient Tachypnea of the Newborn

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1α,25-Dihydroxy-3-epi-vitamin D3, a natural metabolite of 1α,25-dihydroxy vitamin D3: production and biological activity studies in pulmonary alveolar type II cells

Cited by 121 publications

References 23 publications

Vitamin D Receptor-Deficient Mice Fail to Develop Experimental Allergic Asthma

Vitamin D Receptor-Deficient Mice Fail to Develop Experimental Allergic Asthma

Regulation of human pulmonary surfactant protein gene expression by 1α,25-dihydroxyvitamin D3

Maternal Vitamin D Deficiency May be a Risk Factor for Transient Tachypnea of the Newborn

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Regulation of human pulmonary surfactant protein gene expression by 1α,25-dihydroxyvitamin D₃