PMID- 22563925 OWN - NLM STAT- MEDLINE DCOM- 20130429 LR - 20131121 IS - 1399-0039 (Electronic) IS - 0001-2815 (Linking) VI - 80 IP - 2 DP - 2012 Aug TI - In vitro up-regulation of HLA-G using dexamethasone and hydrocortisone in first-trimester trophoblast cells of women experiencing recurrent miscarriage. PG - 126-35 LID - 10.1111/j.1399-0039.2012.01884.x [doi] AB - The trophoblast cells at the maternal-fetal interface express an unusual combination of human leukocyte antigen (HLA)-C, HLA-E and HLA-G. Altered expression of HLA-G on the extravillous cytotrophoblast has been implicated in the etiology of recurrent miscarriages (RMs). We have assessed HLA-G expression in extravillous cytotrophoblast in cell cultures prepared from RM patients and compared with those of first-trimester voluntarily terminated normal pregnancies (control). Glucocorticoids, dexamethasone and hydrocortisone were examined for their role in modulation of the HLA-G expression. HLA-G promoter and 3'UTR variants were investigated for their effect on the transcription of HLA-G. Cultured cytotrophoblast cells from the first-trimester RM patients were treated with dexamethasone and hydrocortisone (dose concentration 0-1000 ng/ml). HLA-G gene transcription was determined by semiquantitative and quantitative real-time polymerase chain reaction (RT-PCR), while protein expression was determined by a specific enzyme-linked immunosorbent assay (ELISA), flow cytometry and western blot analyses. HLA-G polymorphisms were detected by PCR and/or sequence-based typing. Low level of HLA-G was observed in untreated trophoblast cells obtained from RM patients as compared with controls. Upon treatment with glucocorticoids, the expression of HLA-G in these cells was up-regulated in a dose-dependent manner (P < 0.05), with no change in cellular proliferation and viability. There was no significant association between HLA-G polymorphism in RM patients and controls. HLA-G is minimally expressed in cultured trophoblast cells of RM patients. It can be up-regulated upon exposure with both dexamethasone and hydrocortisone. Glucocorticoids have the potential to modulate HLA-G expression in vitro, and can be further examined for their therapeutic applicability in RM. CI - (c) 2012 John Wiley & Sons A/S. FAU - Akhter, A AU - Akhter A AD - Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India. FAU - Faridi, R M AU - Faridi RM FAU - Das, V AU - Das V FAU - Pandey, A AU - Pandey A FAU - Naik, S AU - Naik S FAU - Agrawal, S AU - Agrawal S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120504 PL - England TA - Tissue Antigens JT - Tissue antigens JID - 0331072 RN - 0 (3' Untranslated Regions) RN - 0 (HLA-G Antigens) RN - 7S5I7G3JQL (Dexamethasone) RN - WI4X0X7BPJ (Hydrocortisone) SB - IM MH - 3' Untranslated Regions MH - Abortion, Habitual/*genetics/immunology MH - Adult MH - Dexamethasone/*pharmacology MH - Dose-Response Relationship, Drug MH - Female MH - Gene Expression/drug effects MH - HLA-G Antigens/*genetics/immunology MH - Humans MH - Hydrocortisone/*pharmacology MH - Polymorphism, Genetic MH - Pregnancy MH - Pregnancy Trimester, First MH - Primary Cell Culture MH - Promoter Regions, Genetic MH - Transcription, Genetic MH - Trophoblasts/cytology/*drug effects/metabolism MH - Up-Regulation/drug effects/genetics/immunology EDAT- 2012/05/09 06:00 MHDA- 2013/04/30 06:00 CRDT- 2012/05/09 06:00 PHST- 2012/05/09 06:00 [entrez] PHST- 2012/05/09 06:00 [pubmed] PHST- 2013/04/30 06:00 [medline] AID - 10.1111/j.1399-0039.2012.01884.x [doi] PST - ppublish SO - Tissue Antigens. 2012 Aug;80(2):126-35. doi: 10.1111/j.1399-0039.2012.01884.x. Epub 2012 May 4.