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Ethanol-induced expression of cytokines in a first-trimester trophoblast cell line

      Abstract

      OBJECTIVES: Altered cytokine expression at the fetoplacental interface may be a potential mechanism for the development of fetal immune dysfunction in children with fetal alcohol syndrome. This study was conducted to determine whether first-trimester trophoblasts respond to ethanol exposure by the induction of specific cytokines.
      STUDY DESIGN: HTR-8/SVneo trophoblast cells were cultured in vitro in the presence of either ethanol (0.5% [vol/vol]), lipopolysaccharide (1 μg/mL), or ethanol and lipopolysaccharide. Expression of granulocyte colony–stimulating factor, regulated on activation normal T cell expressed and secreted, and interleukin-6 was examined by Northern analysis and enzyme-linked immunosorbent assay.
      RESULTS: Culture in the presence of ethanol, lipopolysaccharide, or lipopolysaccharide and ethanol resulted in the increased transcription and secretion of granulocyte colony–stimulating factor, regulated on activation normal T cell expressed and secreted, and interleukin-6 at significantly greater levels (P < .01) than control cultures.
      CONCLUSIONS: Human first-trimester trophoblasts express high levels of cytokines when cultured in the presence of ethanol. Trophoblasts may therefore be an important exogenous source of cytokines for the fetus, and altered cytokine levels during early gestation may have an adverse effect on the development of the fetal immune system. (Am J Obstet Gynecol 1998;179:470-5.)

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      References

        • Jones KL
        • Smith DW
        Recognition of the fetal alcohol syndrome in early infancy.
        Lancet. 1973; 2: 999-1001
        • Hanson JW
        • Jones KL
        • Smith DW
        Fetal alcohol syndrome: experience with 41 patients.
        JAMA. 1976; 235: 1458-1460
        • Abel EL
        An update on incidence of FAS: FAS is not an equal opportunity birth defect.
        Neurotoxicology. 1995; 17: 437-443
        • Johnson S
        • Knight R
        • Mariner DJ
        • Steele RW
        Immune deficiency in fetal alcohol syndrome.
        Pediatr Res. 1981; 15: 908-911
        • Weald SJ
        • Frost WW
        Effect of prenatal exposure to ethanol on the development of the thymus.
        Thymus. 1987; 9: 211-215
        • Jerrels TR
        • Peritt D
        • Marietta C
        • Eckardt MJ
        Mechanisms of suppression of cellular immunity induced by alcohol.
        Alcohol Clin Exp Res. 1989; 13: 490-493
        • Grossman A
        • Astley SJ
        • Liggitt HD
        • Clarren SK
        • Shiota F
        • Kennedy B
        • et al.
        Immune function in offspring of nonhuman primates (Macaca nemestrina) exposed weekly to 1.8g/kg ethanol during pregnancy: preliminary observations.
        Alcohol Clin Exp Res. 1993; 17: 822-827
        • Wolcott RM
        • Jennings SR
        • Cheryenak R
        In utero exposure to ethanol affects postnatal development of T- and B-lymphocytes, but not natural killer cells.
        Alcohol Clin Exp Res. 1995; 19: 170-176
        • Chiappelli F
        • Taylor AN
        The fetal alcohol syndrome and fetal alcohol effects on immune competence.
        Alcohol Alcohol. 1995; 30: 259-263
        • Suda T
        • Murray R
        • Guidos C
        • Zlotnik A
        Growth-promoting activity of IL-1α, IL-6, and tumor necrosis factor-α in combination with IL-2, IL-4, or IL-7 on murine thymocytes: differential effects on CD4/CD8 subsets and on CD3+/CD3- double- negative thymocytes.
        J Immunol. 1990; 144: 3039-3045
        • Suda T
        • Zlotnik A
        In vitro induction of CD8 expression on thymic pre-T cells. I. Transforming growth factor-β and tumor necrosis factor-α induce CD8 expression on CD8- thymic subsets including the CD25+CD3–CD4–CD8– pre-T cell subset.
        J Immunol. 1992; 146: 1737-1745
        • Punnonen J
        • de Vries JE
        IL-13 induces proliferation, Ig isotype switching, and Ig synthesis by immature human fetal B cells.
        J Immunol. 1994; 152: 1094-1102
        • Gutierrez-Ramos JC
        • Olsson C
        • Palacios R
        Interleukin (IL1 to IL7) gene expression in fetal liver and bone marrow stromal cell clones: cytokine-mediated positive and negative regulation.
        Exp Hematol. 1992; 20: 986-990
        • Godfrey DI
        • Kennedy J
        • Gately MK
        • Hakimi J
        • Hubbard BR
        • Zlotnik A
        IL-12 influences intrathymic T cell development.
        J Immunol. 1994; 152: 2729-2735
        • Suda T
        • Zlotnik A
        IL-7 maintains the T cell precursor potential of CD3–CD4–CD8– thymocytes.
        J Immunol. 1991; 146: 3068-3073
        • Gonik B
        • Rachmilewitz J
        • Hochberg A
        • Goshen R
        • deGroot N
        Induction of tumor necrosis factor and interleukin-6 mRNA in human cytotrophoblast cells exposed to lipopolysaccharide.
        Infect Dis Obstet Gynecol. 1994; 2: 3-9
        • Svinarich DM
        • Bitonti OM
        • Romero R
        • Gonik B
        Induction and post-translational expression of cytokines in a first-trimester trophoblast cell line by lipopolysaccharide.
        Am J Obstet Gynecol. 1996; 175: 970-973
        • Svinarich DM
        • Bitonti OM
        • Araneda H
        • Romero R
        • Gonik B
        Induction and postranslational expression of G-CSF and RANTES in a first trimester trophoblast cell line by lipopolysaccharide.
        Am J Reprod Immunol. 1996; 36: 256-259
        • Medlock ES
        • Kaplan DL
        • Cecchine M
        • Ulich TR
        • Castello J
        • Andresen J
        Granulocyte colony–stimulating factor crosses the placenta and stimulates fetal rat granulopoiesis.
        Blood. 1993; 81: 916-922
        • Gutierrez-Ramos JC
        • Olsson C
        • Palacios R
        Interleukin (IL1 to IL7) gene expression in fetal liver and bone marrow stromal clones: cytokine-mediated positive and negative regulation.
        Exp Hematol. 1992; 20: 986-990
        • Moore NC
        • Anderson G
        • Smith CA
        • Owen JJT
        • Jenkinson EJ
        Analysis of cytokine gene expression in subpopulations of freshly isolated thymocytes and thymic stromal cells using semiquantitative polymerase chain reaction.
        Eur J Immunol. 1993; 23: 922-927
        • Miller MD
        • Krangel MS
        Biology and biochemistry of the chemokines: a family of chemotactic and inflammatory cytokines.
        Crit Rev Immunol. 1992; 12: 17-46
        • Graham CH
        • Hawley TS
        • Hawley RG
        • MacDougall JR
        • Kerbel RS
        • Khoo N
        • et al.
        Establishment and characterization of first trimester human trophoblast cells with extended lifespan.
        Exp Cell Res. 1993; 206: 204-211
        • Dudley DJ
        • Trautman MS
        • Mitchell MD
        Inflammatory mediators regulate interleukin-8 production by cultured gestational tissues: evidence for a cytokine network at the chorio-decidual interface.
        J Clin Endocrinol Metab. 1993; 76: 404-410
        • Wegman TG
        • Guilbert LJ
        Immune signaling at the maternal-fetal interface and trophoblast differentiation.
        Dev Comp Immunol. 1992; 16: 425-430