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Amniotic Fluid Soluble Myeloid Differentiation‐2 ( sMD ‐2) as Regulator of Intra‐amniotic Inflammation in Infection‐induced Preterm Birth
Author(s) -
Dulay Antonette T.,
Buhimschi Catalin S.,
Zhao Guomao,
Oliver Emily A.,
AbdelRazeq Sonya S.,
Shook Lydia L.,
Bahtiyar Mert O.,
Buhimschi Irina A.
Publication year - 2015
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.12362
Subject(s) - amniotic fluid , amniocentesis , biology , inflammation , andrology , fetus , immunology , medicine , pregnancy , prenatal diagnosis , genetics
Problem TLR 4 mediates host responses to pathogens through a mechanism that involves protein myeloid differentiation‐2 ( MD ‐2) and its soluble form sMD ‐2. The role of sMD 2 in intra‐amniotic inflammation‐induced preterm birth has not been previously explored. Method of study Human amniotic fluid ( AF ) sMD ‐2 was studied by Western blotting in 152 AF samples of patients who had an amniocentesis to rule‐out infection (yes infection, n = 50; no infection, n = 50) or women with normal pregnancy outcome (second trimester genetic karyotyping, n = 26; third trimester lung maturity testing, n = 26). Histological localization and mRNA expression of MD 2 in fetal membranes were studied by immunohistochemistry and RT ‐ PCR . The ability of fetal membrane to release sMD ‐2 and inflammatory cytokines was studied in vitro . Results Human AF contains three sMD ‐2 proteoforms whose levels of expression were lower at term. Intra‐amniotic infection upregulated sMD ‐2. MD ‐2 mRNA and immunohistochemistry findings concurred. In vitro , LPS and monensin increased, while cycloheximide decreased sMD ‐2 production. Recombinant sMD ‐2 modulated TNF ‐α and IL ‐6 levels in a dose‐ and time‐dependent fashion. Conclusion sMD 2 proteoforms are constitutively present in human AF . The intensity of the intra‐amniotic inflammatory response to bacteria or perhaps to other TLR 4 ligands may be facilitated through synthesis and release of sMD 2 by the amniochorion.