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Calcitriol reduces eosinophil cytolysis and release of cytotoxic granules in vitro

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Epidemiological studies show a strong correlation between vitamin D deficiency and asthma severity... 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 alone yielded similar eosinophil survival rates (Fig2.4.5 ± 1.5%, n = 11) after 7 days compared to control media (Fig2. 2.1 ± 2.1%, n = 11)... In contrast, calcitriol potentiated the survival effect of IL-5 starting from day 7... Cells treated with IL-5 alone showed increased necrosis from day 7 onward with 32% additional necrotic eosinophils at day 14, compared to the combined treatment... As cell debris increased in correlation with necrosis (Fig3 A&B.), low-SSC/FSC events stained positive for CD63 and EPX confirming whole, intact crystalloid granules along with free EPX in media (Fig4.)... Moreover, EPX activity in media was reduced on days 4 and 7 following calcitriol and IL-5 treatment (Fig5.)... Overall, reduced spontaneous EPX release strongly correlated with increased eosinophil survival (Fig6. r = 0.96, n = 4-11)... 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.

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Mentions: Eosinophil survival increased after 24 h of calcitriol treatment in a dose-dependent manner (Fig1. n = 5). Calcitriol alone yielded similar eosinophil survival rates (Fig2.4.5 ± 1.5%, n = 11) after 7 days compared to control media (Fig2. 2.1 ± 2.1%, n = 11). In contrast, calcitriol potentiated the survival effect of IL-5 starting from day 7. At 14 days, 66 ± 7% of eosinophils were still intact when treated with calcitriol and IL-5, compared to IL-5 alone (Fig2. 34 ± 8%, p < 0.05, n = 4). Cells treated with IL-5 alone showed increased necrosis from day 7 onward with 32% additional necrotic eosinophils at day 14, compared to the combined treatment. As cell debris increased in correlation with necrosis (Fig3 A&B.), low-SSC/FSC events stained positive for CD63 and EPX confirming whole, intact crystalloid granules along with free EPX in media (Fig4.). Moreover, EPX activity in media was reduced on days 4 and 7 following calcitriol and IL-5 treatment (Fig5.). Overall, reduced spontaneous EPX release strongly correlated with increased eosinophil survival (Fig6. r2 = 0.96, n = 4-11).


Calcitriol reduces eosinophil cytolysis and release of cytotoxic granules in vitro
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4126033&req=5

Mentions: Eosinophil survival increased after 24 h of calcitriol treatment in a dose-dependent manner (Fig1. n = 5). Calcitriol alone yielded similar eosinophil survival rates (Fig2.4.5 ± 1.5%, n = 11) after 7 days compared to control media (Fig2. 2.1 ± 2.1%, n = 11). In contrast, calcitriol potentiated the survival effect of IL-5 starting from day 7. At 14 days, 66 ± 7% of eosinophils were still intact when treated with calcitriol and IL-5, compared to IL-5 alone (Fig2. 34 ± 8%, p < 0.05, n = 4). Cells treated with IL-5 alone showed increased necrosis from day 7 onward with 32% additional necrotic eosinophils at day 14, compared to the combined treatment. As cell debris increased in correlation with necrosis (Fig3 A&B.), low-SSC/FSC events stained positive for CD63 and EPX confirming whole, intact crystalloid granules along with free EPX in media (Fig4.). Moreover, EPX activity in media was reduced on days 4 and 7 following calcitriol and IL-5 treatment (Fig5.). Overall, reduced spontaneous EPX release strongly correlated with increased eosinophil survival (Fig6. r2 = 0.96, n = 4-11).

View Article: PubMed Central - HTML

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Epidemiological studies show a strong correlation between vitamin D deficiency and asthma severity... 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 alone yielded similar eosinophil survival rates (Fig2.4.5 ± 1.5%, n = 11) after 7 days compared to control media (Fig2. 2.1 ± 2.1%, n = 11)... In contrast, calcitriol potentiated the survival effect of IL-5 starting from day 7... Cells treated with IL-5 alone showed increased necrosis from day 7 onward with 32% additional necrotic eosinophils at day 14, compared to the combined treatment... As cell debris increased in correlation with necrosis (Fig3 A&B.), low-SSC/FSC events stained positive for CD63 and EPX confirming whole, intact crystalloid granules along with free EPX in media (Fig4.)... Moreover, EPX activity in media was reduced on days 4 and 7 following calcitriol and IL-5 treatment (Fig5.)... Overall, reduced spontaneous EPX release strongly correlated with increased eosinophil survival (Fig6. r = 0.96, n = 4-11)... 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.

No MeSH data available.