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Modulation of trophoblast function by concurrent hyperglycemia and antiphospholipid antibodies is in part TLR 4‐dependent
Author(s) -
LeonMartinez Daisy,
Mulla Melissa J.,
Han Christina S.,
Chamley Lawrence W.,
Abrahams Vikki M.
Publication year - 2018
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/aji.13045
Subject(s) - trophoblast , preeclampsia , inflammasome , endocrinology , medicine , diabetes mellitus , placenta , uric acid , biology , andrology , pregnancy , receptor , fetus , genetics
Problem While diabetes and APS are individually associated with increased risk of poor perinatal outcomes, in particular preeclampsia, recent studies have demonstrated an association between concurrent aPL and diabetes leading to an increased risk of pregnancy morbidity. Hyperglycemia and aPL have independently been shown to alter human trophoblast function by inducing a pro‐inflammatory, anti‐angiogenic, and antimigratory response. However, little is known about the effects of concurrent hyperglycemia and aPL on trophoblast function. Method of study A human first‐trimester extravillous trophoblast cell line was exposed to glucose at 5 mmol/L (normoglycemia) or 25 mmol/L (hyperglycemia), all in the presence or absence of low‐dose aPL or control IgG. For some experiments, the TLR 4 antagonist, LPS ‐ RS , was included. Cell culture supernatants were measured for inflammatory IL ‐1β and IL ‐8, and angiogenic Pl GF , sF lt‐1, and sE ndoglin by ELISA . Inflammasome‐associated uric acid was measured using a bioassay; caspase‐1 was measured using an activity assay. Trophoblast migration was quantified using a two‐chamber colorimetric assay. Results Compared to excess glucose alone, combination excess glucose and low‐dose aPL (a) further augmented trophoblast inflammatory IL ‐1β, inflammasome‐associated uric acid and caspase‐1, and pro‐angiogenic Pl GF ; (b) dampened trophoblast inflammatory IL ‐8, anti‐angiogenic sE ndoglin, and sF lt‐1; and (c) further reduced trophoblast migration. Conclusion Our findings indicate that while concurrent aPL and hyperglycemia are overall detrimental to trophoblast function, the presence of two simultaneous insults triggers some protective effects.