ABSTRACT
Background: Vitamin D insufficiency and deficiency can be associated with adverse effects on fetus and pregnancy outcomes. This study aimed at evaluating the effect of 1,25VitD3 on specific transcription factor and markers of Tregs and T helper 17 (Th17) cells in peripheral blood mononuclear cells (PBMCs) of women with unexplained recurrent pregnancy loss (URPL) as a case group and PBMCs of healthy women as a control group. Methods: Samples from 20 non-pregnant patients with a history of URPL were compared to 20 normal non-pregnant women. PBMCs were divided into three wells for each subject in the presence of 1,25VitD3 (50 nM, for 16 hours), phytohemagglutinin (10 µM; positive control), and without any treatment (negative control). By Real-time PCR (Taqman assay), specific transcription factors of Tregs and Th17 cells, forkhead box P3 (FOXP3), retinoic acid-related orphan receptor γt (ROR-γt), glucocorticoid-induced tumor necrosis factor receptor-related (GITR), and CTLA-4 mRNA expressions in two groups were measured. Results: FOXP3/ROR-γt mRNA expression in PBMCs decreased significantly in women experiencing URPL compared to the control group (p = 0.0001). Although 1,25VitD3 (50 nM) increased FOXP3 gene expression (p = 0.0001), it did not significantly affect ROR-γt gene expression. Besides, 1,25VitD3 treatment significantly increased FOXP3/ROR-γt mRNA expression from baseline in PBMCs of the fetal loss group compared to that of the control group (p = 0.01). The 1,25VitD3 also increased GITR gene expression (p = 0.017) in PBMCs of URPL women compared to the controls. Conclusion: Vitamin D deficiency may be a contributor to recurrent pregnancy loss and suggests that the supplementation of women with Vitamin D pre-pregnancy may be protective against URPL via affecting Tregs signature genes, FOXP3 and GITR.
Subject(s)
Abortion, Habitual/genetics , CTLA-4 Antigen/genetics , Calcitriol/pharmacology , Forkhead Transcription Factors/genetics , Gene Expression Regulation , Glucocorticoid-Induced TNFR-Related Protein/genetics , Leukocytes, Mononuclear/metabolism , Nuclear Receptor Subfamily 1, Group F, Member 3/genetics , Abortion, Habitual/blood , Abortion, Habitual/immunology , Biomarkers/blood , CTLA-4 Antigen/metabolism , Case-Control Studies , Female , Forkhead Transcription Factors/metabolism , Gene Expression Regulation/drug effects , Glucocorticoid-Induced TNFR-Related Protein/metabolism , Gonadal Steroid Hormones/blood , Humans , Leukocytes, Mononuclear/drug effects , Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism , Pregnancy , T-Lymphocytes, Regulatory/immunology , Th17 Cells/immunology , Young AdultABSTRACT
Naringin, a well-known flavanone glycoside found in grapefruit and other citrus fruits, was determined to be an effective anti-inflammatory compound. We investigated the effect of naringin on the key mediators of arthritic inflammation, namely T cell subsets, CD4(+)GITR(+) expressing cells, CD4(+)CD25(+)Foxp3(+) (Treg), Th1/Th2 cytokines and inflammatory mediators. We treated Balb/c mice (p.o.) with naringin (20, 40 and 80 mg/kg) for 14 days. Compared with the vehicle-treated and arthritic-control mice, the naringin treatment demonstrated a considerable decrease in the level of T cells, CD4(+)GITR(+), Th1 cytokine and inflammatory mediator expressions. In contrast, naringin treatment resulted in significantly up-regulated Treg and Th2 cytokine levels. Therefore, the naringin-induced inhibition of the T cells, various pro-inflammatory cytokines and inflammatory mediators that facilitate cellular infiltration into the joints might have contributed to its anti-arthritic activity. Our data suggest that naringin diminished the AIA in mice and it could be a potential alternative/adjunct treatment for RA.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Arthritis/therapy , Autoimmune Diseases/therapy , Citrus paradisi/chemistry , Flavanones/therapeutic use , T-Lymphocyte Subsets/drug effects , T-Lymphocytes, Regulatory/drug effects , Animals , Arthritis/immunology , Autoimmune Diseases/immunology , CD4 Antigens/metabolism , Cells, Cultured , Cytokines/metabolism , Disease Progression , Female , Forkhead Transcription Factors/metabolism , Glucocorticoid-Induced TNFR-Related Protein/metabolism , Inflammation Mediators/metabolism , Interleukin-2 Receptor alpha Subunit/metabolism , Mice , Mice, Inbred BALB C , T-Lymphocyte Subsets/immunology , T-Lymphocytes, Regulatory/immunology , Th1-Th2 BalanceABSTRACT
Proanthocyanidins are the most abundant phenolic compounds and have been reported to exert anti-inflammatory actions. The aim of this study was to investigate the effects of grape seed proanthocyanidin extract (GSPE) in a mouse model of carrageenan-induced pleurisy. Following the induction of pleurisy using λ-carrageenan (Cg, 1 %), GSPE (25, 50 and 100 mg/kg) was administered per-oral (p.o.), and the glucocorticoid-induced tumour necrosis factor receptor (GITR), IL-17A expressing cells and other markers, such as cytokines (Th1/Th2 and Th17), were studied. We evaluate the effects of GSPE on the mRNA expression of pro-inflammatory and anti-inflammatory mediators. The results illustrated that the cell numbers of IL-17A and GITR expressing cells and the cytokine levels in Th1/Th17 cells were markedly increased in the Cg-group, whereas the cytokines produced by Th2 cells were significantly decreased in the same group. Treatment with GSPE reversed these effects. Histological examinations revealed anti-inflammatory effects of GSPE.