Researchers from the University of California, Los Angeles (UCLA) report that production of an antimicrobial protein called cathelicidin was stimulated when trophoblasts - cells that develop to make up a major part of the placenta – were exposed to the active form of vitamin D (1,25(OH)2D).
The study, published online ahead of print in the journal Biology of Reproduction, claims to be the first to report such observations.
“Although the precise function of vitamin D within the placenta remains to be defined, data from this study suggest that local synthesis of active 1,25(OH)2D may play a key role in placental innate immunity,” wrote the researchers, led by Martin Hewison from UCLA's David Geffen School of Medicine.
“We further postulate that improvement of maternal vitamin D status through dietary supplementation may act to potentiate placental innate immune responses during pregnancy.”
Vitamin D refers to two biologically inactive precursors - D3, also known as cholecalciferol, and D2, also known as ergocalciferol. The former, produced in the skin on exposure to UVB radiation (290 to 320 nm), is said to be more bioactive.
Both D3 and D2 precursors are hydroxylated in the liver and kidneys to form 25- hydroxyvitamin D (25(OH)D), the non-active 'storage' form, and 1,25-dihydroxyvitamin D (1,25(OH)2D), the biologically active form that is tightly controlled by the body.
Hewison and his co-workers exposed the human trophoblast cells to 1,25(OH)2D at doses ranging from 1 to 100 micromoles. A dose-dependent response was observed with respect to the induction of cathelicidin.
Moreover, exposure to either 25(OH)D or 1,25(OH)2D both produced a “significantly enhanced antibacterial responses in trophoblastic cells”, said the researchers. Indeed, cells infected with Escherichia coli (E. coli) showed reduced numbers of E.coli when treated with both 25OHD (49.6 per cent) or 1,25(OH)2D (45.4 per cent).
A reduction in cell death as a result of E. coli exposure was also observed after exposing the cells to both forms of the vitamin.
"Data presented here show for the first time that induction of trophoblastic cathelicidin may be a key facet of placental innate immunity,” wrote the researchers.
“Importantly, we also demonstrate that expression of cathelicidin by trophoblastic cells is potently enhanced following intracrine activation of vitamin D.
“Given that circulating levels of the prohormone form of vitamin D (25OHD) vary significantly in pregnant women, we hypothesize that placental capacity to synthesize cathelicidin and mount effective innate immune responses may also be subject to substantial variation.”
Calls to raise levels
Eighteen scientists from UC recently issued a “call to action” to raise the recommended daily intakes of vitamin D to 2,000 International Units (IU). This echoed a number of others from leading academics across the globe, and may increase the need for policy makers to review current guidelines for the vitamin. Such increases could also open opportunities for food fortification and supplements.
Current recommended daily intakes (RDIs) of vitamin D are 200 IU for people up to 50 years of age, 400 IU for people between 51 and 70, and 600 IU for over the 70s years.
Source: Biology of ReproductionPublished online ahead of print, doi: 10.1095/biolreprod.108.073577“Vitamin D induces innate antibacterial responses in human trophoblasts via an intracrine pathway”Authors: N. Liu, A. T. Kaplan, J. Low, L. Nguyen, G. Y. Liu, O. Equils, M. Hewison.