Decreased anti-inflammatory responses to vitamin D in neonatal neutrophils.
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.
Division of Neonatology, Department of Pediatrics, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08901, USA.
Daniel
D
Hirsch
Faith E
FE
Archer
Meera
M
Joshi-Kale
Anna M
AM
Vetrano
Barry
B
Weinberger
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002112:Calcifediol / Q000378:metabolism; D054407:Chemokine CCL4 / Q000096:biosynthesis; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007231:Infant, Newborn; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D008954:Models, Biological; D009504:Neutrophils / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D014807:Vitamin D / Q000737:chemistry* / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D054407:Chemokine CCL4; D042461:Vascular Endothelial Growth Factor A; D014807:Vitamin D; D006861:Hydrogen Peroxide; D002112:Calcifediol