119: The effect of 1,25-dihydroxyvitamin D3 (1,25[OH2]D3), on lipopolysacharide(LPS) induced cytokine expression by human decidual cells

Abstract

ObjectiveDecidual inflammation may contribute to the cascade of events that culminate in preterm labor and delivery. The anti-inflammatory effect of vitamin D is well established. There is compelling evidence for increased frequency of spontaneous preterm birth with vitamin D deficiency. The purpose of this study was to evaluate the ability of the active form of vitamin D, 1,25[OH2]D3, to modify the inflammatory response of human decidual cells exposed to LPS.Study designDecidua was scraped from the membranes from the placentae of 4 women undergoing term prelabor cesarean section . Decidual cells were obtained through enzymatic digestion and Percoll gradient purification. Cells were cultured to confluence and pretreated with 1,25[OH2]D3 for 24 hours before LPS administration. mRNA was then extracted and real time PCR was used to compare expression of interleukin(IL)-1α, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-α(TNF-α) and IL-1 receptor antagonist(RA) mRNA relative to GAPDH.ResultsPretreatment with 1,25[OH2]D3 decreased the relative basal expression of IL-6 and IL-8 mRNA (p<0.01). IL-8 mRNA was significantly decreased in the LPS stimulated cultures pretreated with 1,25[OH2]D3 (p<0.05) versus LPS stimulation alone. In regards to IL-1α, IL-4, IL-10, TNF-α, and IL-1RA mRNA production, trends toward reduced expression were noted in all the cultures pretreated with 1,25[OH2]D3, yet statistically significant changes were not identified.ConclusionVitamin D abrogated the ability of LPS to stimulate IL-8 expression in human cultured decidual cells. This change in expression could account for the decreased frequency of spontaneous preterm birth in patients with sufficiency of vitamin D. Future studies exploring the possible therapeutic anti-inflammatory effects of vitamin D are warranted. ObjectiveDecidual inflammation may contribute to the cascade of events that culminate in preterm labor and delivery. The anti-inflammatory effect of vitamin D is well established. There is compelling evidence for increased frequency of spontaneous preterm birth with vitamin D deficiency. The purpose of this study was to evaluate the ability of the active form of vitamin D, 1,25[OH2]D3, to modify the inflammatory response of human decidual cells exposed to LPS. Decidual inflammation may contribute to the cascade of events that culminate in preterm labor and delivery. The anti-inflammatory effect of vitamin D is well established. There is compelling evidence for increased frequency of spontaneous preterm birth with vitamin D deficiency. The purpose of this study was to evaluate the ability of the active form of vitamin D, 1,25[OH2]D3, to modify the inflammatory response of human decidual cells exposed to LPS. Study designDecidua was scraped from the membranes from the placentae of 4 women undergoing term prelabor cesarean section . Decidual cells were obtained through enzymatic digestion and Percoll gradient purification. Cells were cultured to confluence and pretreated with 1,25[OH2]D3 for 24 hours before LPS administration. mRNA was then extracted and real time PCR was used to compare expression of interleukin(IL)-1α, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-α(TNF-α) and IL-1 receptor antagonist(RA) mRNA relative to GAPDH. Decidua was scraped from the membranes from the placentae of 4 women undergoing term prelabor cesarean section . Decidual cells were obtained through enzymatic digestion and Percoll gradient purification. Cells were cultured to confluence and pretreated with 1,25[OH2]D3 for 24 hours before LPS administration. mRNA was then extracted and real time PCR was used to compare expression of interleukin(IL)-1α, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-α(TNF-α) and IL-1 receptor antagonist(RA) mRNA relative to GAPDH. ResultsPretreatment with 1,25[OH2]D3 decreased the relative basal expression of IL-6 and IL-8 mRNA (p<0.01). IL-8 mRNA was significantly decreased in the LPS stimulated cultures pretreated with 1,25[OH2]D3 (p<0.05) versus LPS stimulation alone. In regards to IL-1α, IL-4, IL-10, TNF-α, and IL-1RA mRNA production, trends toward reduced expression were noted in all the cultures pretreated with 1,25[OH2]D3, yet statistically significant changes were not identified. Pretreatment with 1,25[OH2]D3 decreased the relative basal expression of IL-6 and IL-8 mRNA (p<0.01). IL-8 mRNA was significantly decreased in the LPS stimulated cultures pretreated with 1,25[OH2]D3 (p<0.05) versus LPS stimulation alone. In regards to IL-1α, IL-4, IL-10, TNF-α, and IL-1RA mRNA production, trends toward reduced expression were noted in all the cultures pretreated with 1,25[OH2]D3, yet statistically significant changes were not identified. ConclusionVitamin D abrogated the ability of LPS to stimulate IL-8 expression in human cultured decidual cells. This change in expression could account for the decreased frequency of spontaneous preterm birth in patients with sufficiency of vitamin D. Future studies exploring the possible therapeutic anti-inflammatory effects of vitamin D are warranted. Vitamin D abrogated the ability of LPS to stimulate IL-8 expression in human cultured decidual cells. This change in expression could account for the decreased frequency of spontaneous preterm birth in patients with sufficiency of vitamin D. Future studies exploring the possible therapeutic anti-inflammatory effects of vitamin D are warranted.