Natural Antimicrobial Peptide Regulation by Cytokines and Vitamin D in human vaginal epithelial (VK2/E6E7) cells

TY - JOUR

T1 - Natural Antimicrobial Peptide Regulation by Cytokines and Vitamin D in human vaginal epithelial (VK2/E6E7) cells

AU - Chin-Smith, Evonne

PY - 2012

Y1 - 2012

N2 - Introduction: Natural antimicrobial peptides (NAPs) are an important part of the innate immune defences against bacterial infection and production of NPAs can be stimu- lated by 1,25-dihydroxyvitamin D3 (VitD3). The role of NAPs in infection-associated preterm birth is still unclear. Previously, we identified two cytokines (GM-CSF and MCP1) that were elevated in cervico-vaginal fluid of women at high risk of spontaneous preterm birth (STPB). This study assessed the effect of GM-CSF, MCP1 and IL-1b and VitD3 and calcipotriol on NAP expression in human vaginal epithelial cells. Methods: VK2/E6E7 cells (~80% confluence, growth factor deprived) were treated with IL-1b, MCP-1, GM-CSF (1 or 10ng/ml for 6 h, n = 6), Vit D or calcipotriol (10 )9 –10 )6 M for 6 h, n = 3). RNA was extracted and NAP (SKALP, SLPI, hBD2) mRNA expression determined by qPCR. Data were analysed using ANOVA with Bonferroni’s multiple comparison test, or linear regression. Results: SKALP and hBD2 were significantly increased by IL-1b (p < 0.05 and p < 0.01 respectively). GM-CSF inhib- ited SKALP mRNA expression (p < 0.05). Both VitD3 and calcipotriol increased SKALP, hBD2 and SLPI mRNA expression in a concentration dependent manner (p < 0.01). MCP1 had no effect on any of the NAPs assessed. Conclusion: GM-CSF suppression of SKALP provides a novel mechanism may explain, in part, impaired immune defences against ascending infection in women at risk of preterm labour. The evidence that VitD3 increases NAP expression in VK2/E6E7 indicates that vitamin D supple- mentation could be considered as a potential therapy to sti- mulate immune defences in women at risk of spontaneous preterm birth.

AB - Introduction: Natural antimicrobial peptides (NAPs) are an important part of the innate immune defences against bacterial infection and production of NPAs can be stimu- lated by 1,25-dihydroxyvitamin D3 (VitD3). The role of NAPs in infection-associated preterm birth is still unclear. Previously, we identified two cytokines (GM-CSF and MCP1) that were elevated in cervico-vaginal fluid of women at high risk of spontaneous preterm birth (STPB). This study assessed the effect of GM-CSF, MCP1 and IL-1b and VitD3 and calcipotriol on NAP expression in human vaginal epithelial cells. Methods: VK2/E6E7 cells (~80% confluence, growth factor deprived) were treated with IL-1b, MCP-1, GM-CSF (1 or 10ng/ml for 6 h, n = 6), Vit D or calcipotriol (10 )9 –10 )6 M for 6 h, n = 3). RNA was extracted and NAP (SKALP, SLPI, hBD2) mRNA expression determined by qPCR. Data were analysed using ANOVA with Bonferroni’s multiple comparison test, or linear regression. Results: SKALP and hBD2 were significantly increased by IL-1b (p < 0.05 and p < 0.01 respectively). GM-CSF inhib- ited SKALP mRNA expression (p < 0.05). Both VitD3 and calcipotriol increased SKALP, hBD2 and SLPI mRNA expression in a concentration dependent manner (p < 0.01). MCP1 had no effect on any of the NAPs assessed. Conclusion: GM-CSF suppression of SKALP provides a novel mechanism may explain, in part, impaired immune defences against ascending infection in women at risk of preterm labour. The evidence that VitD3 increases NAP expression in VK2/E6E7 indicates that vitamin D supple- mentation could be considered as a potential therapy to sti- mulate immune defences in women at risk of spontaneous preterm birth.

U2 - 10.1111/j.1471-0528.2012.03315.x

DO - 10.1111/j.1471-0528.2012.03315.x

M3 - Meeting abstract

SN - 0306-5456

VL - 119

SP - e2-e3

JO - British Journal of Obstetrics and Gynaecology

JF - British Journal of Obstetrics and Gynaecology

IS - 6

ER -