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Decreased anti-inflammatory responses to vitamin D in neonatal neutrophils
Daniel Hirsch1, Faith E Archer, Meera Joshi-Kale
1Division of Neonatology, Department of Pediatrics, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08901, USA.
Insights
Vitamin D (1,25-dihydroxyvitamin D3) normally suppresses neutrophil activation, but this anti-inflammatory effect is impaired in newborns due to reduced vitamin D receptor expression, potentially contributing to neonatal inflammation.
Area of Science:
- Immunology
- Neonatal Medicine
- Endocrinology
Background:
- Neutrophil activity is prolonged in newborns.
- This suggests reduced responses to immunosuppressive factors like 1,25-dihydroxyvitamin D3 (1,25-vit D3).
Purpose of the Study:
- To investigate if 1,25-vit D3 suppresses neutrophil activation.
- To determine if this response is impaired in neonatal neutrophils.
Main Methods:
- Compared 1,25-vit D3 effects on lipopolysaccharide (LPS)-induced neutrophil activation in adult and neonatal cells.
- Measured expression of vitamin D receptor (VDR) and 1α-hydroxylase in neutrophils.
- Assessed inflammatory mediator and enzyme expression (MIP-1β, VEGF, COX-2, 5-LOX).
Main Results:
- 1,25-vit D3 decreased inflammatory markers in adult neutrophils but not neonatal ones.
- Neonatal neutrophils showed reduced VDR and 1α-hydroxylase expression.
- 1,25-vit D3 induced VDR expression in adult neutrophils, but not neonatal.
- Vitamin D insensitivity did not affect respiratory burst in either group.
Conclusions:
- Neonatal neutrophils exhibit impaired anti-inflammatory responses to 1,25-vit D3.
- Reduced VDR and 1α-hydroxylase expression likely underlies this insensitivity.
- This neonatal vitamin D insensitivity may contribute to chronic inflammation.
Abstract:
Neutrophil activity is prolonged in newborns, suggesting decreased exposure and/or responses to immunosuppressive modulators, such as 1,25-hydroxyvitamin D(3) (1,25-vit D(3)). We hypothesized that 1,25-vit D(3) suppresses neutrophil activation and that this response is impaired in newborns. Consistent with this, 1,25-vit D(3) decreased LPS-induced expression of macrophage inflammatory protein-1β and VEGF in adult, but not neonatal, neutrophils. Expression of vitamin D receptor (VDR) and 25-hydroxyvitamin D(3)-1α-hydroxylase was reduced in neonatal, relative to adult neutrophils. Moreover, 1,25-vit D(3) induced VDR gene expression in activated adult, but not neonatal, neutrophils. 1,25-vit D(3) also suppressed expression of cyclooxygenase-2 and induced expression of 5-lipoxygenase in LPS-exposed adult neutrophils, while neonatal cells were not affected. 1,25-vit D(3) had no effect on respiratory burst in either adult or neonatal cells. Anti-inflammatory activity of vitamin D is impaired in neonatal neutrophils, and this may be due to decreased expression of VDR and 1α-hydroxylase. Insensitivity to 1,25-vit D(3) may contribute to chronic inflammation in neonates.
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