Volume 10 Supplement 1
Calcitriol reduces eosinophil cytolysis and release of cytotoxic granules in vitro
© Ethier et al; licensee BioMed Central Ltd. 2014
Published: 3 March 2014
Epidemiological studies show a strong correlation between vitamin D deficiency and asthma severity. Genetic studies have identified vitamin D receptor polymorphisms as a risk factor for asthma in diverse human populations. Calcitriol (1,25-dihydroxyvitamin D3), the physiologically active metabolite of mammalian vitamin D, is able to modulate receptor and cytokine expression as well as cell differentiation and maturation of various leukocytes in an anti-inflammatory manner. Despite the role of eosinophils in allergic asthma pathology, little is known about the effects of calcitriol on eosinophil biology. Calcitriol has a direct modulatory effect on eosinophil survival and effector functions in vitro.
Human peripheral blood eosinophils from atopic donors were isolated and incubated with calcitriol (VD) and interleukin-5 (IL-5). Dose-response assays tested physiological doses of calcitriol (0.01-100 nM). The potentiating effect of calcitriol (10 nM) on eosinophil survival with IL-5 (1 ng/mL) was investigated on a 14-day time course. Viability/apoptosis/necrosis levels were obtained using an Annexin-V/PI flow cytometry assay. Eosinophil crystalloid granules and EPX release were measured by CD63 and EPX monoclonal antibody staining using flow cytometry. EPX activity was determined using an OPD substrate colorimetric assay.
These findings support the hypothesis that calcitriol plays an anti-inflammatory role by decreasing cytotoxic granule release into airway mucosal tissues during allergic inflammatory responses, therefore reducing mucosal inflammation and tissue damage.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.