Pre-B-cell colony-enhancing factor, a novel cytokine of human fetal membranes
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Fig. 1
Examples of immunostaining for PBEF in the human fetal membranes. A, Early pregnancy (87 days' gestation) and a serial section (B) as control, with nonimmune IgG at the same concentration as anti-PBEF in A. (Original magnification ×318). Positive staining in amniotic epithelium (a) and mesenchyme (m) cells. C, Fetal membrane from a patient delivered at preterm after labor with no evidence of chorioamnionitis. (Original magnification ×300.) Positive staining in the amniotic epithelium, chorionic cytotrophoblast, and decidua (not shown). D, Fetal membrane from a patient after normal term vaginal delivery. (Original magnification ×260.) Positive perinuclear staining can be seen in the cells of the amniotic epithelium and the mesenchymal cells of the connective tissue directly beneath. The cells of the chorionic cytotrophoblast have positively stained cytoplasm and the decidual cells stained similarly but are not visible in this section.
Fig. 2
Quantitative Northern analysis of PBEF gene expression in the fetal membranes and placenta. The three PBEF transcripts are shown above their quantitation, expressed as counts per microgram. Asterisk, There was significantly more (P <.01) PBEF expressed in the amnion compared with the chorion or placenta.
Fig. 3
The expression of PBEF, IL-6, and IL-8 in the human fetal membranes: open bar, no labor; solid bar, labor. A, PBEF expression was up-regulated by labor, but this did not reach significance at either gestational age. B, IL-6 expression after labor and delivery was significantly up-regulated both at preterm and term compared with the nonlabored tissues of matched gestational age (asterisk, P <.01 in each case). IL-6 expression at preterm labor was (two asterisks, significantly higher than that at term labor, P <.05). The correlation between PBEF and IL-6 expression (r = 0.64) was significant (P <.1) and that between PBEF and IL-8 expression (r = 0.86) was also extremely significant(P <.0001). C, IL-8 expression was increased after labor both at preterm and term, where the latter reached statistical significance (asterisk, P <.05) compared with the nonlabored tissues of matched gestational age.
Fig. 4
The effect of rhPBEF treatment on the expression of IL-6 and IL-8 in amniotic epithelial (WISH) cells. A, The dose-dependant increase in IL-6 gene expression after treatment with rhPBEF at 1, 10, and 100 ng/mL for 4 hours. Asterisk, Significantly (P <.05) increased expression compared with the control. B, The dose-dependent effect of rhPBEF on IL-8 gene expression: 10 ng/mL rhPBEF caused a significant (P <.01) increase in IL-8 gene expression after 4 hours. C, The effect of rhPBEF on IL-8 protein expression in the media after 24 hours of treatment measured by ELISA: 10 ng/mL rhPBEF caused a significant (P <.01) increase compared with the control.
Fig. 5
The effect of rhPBEF treatment on the expression of IL-8 in fetal membrane explants. RhPBEF (100 ng/mL) caused a significant (asterisk, P <.05) increase in IL-8 gene expression after 4 hours of treatment compared with the control.
Fig. 6
Diagrammatic summary of the possible relationships between PBEF, IL-6, and IL-8 and their controls by mechanical stimulation, by infectious stimulation, and by labor.
Abstract
Objective: Our purpose was to determine whether pre-B-cell colony-enhancing factor (PBEF) is expressed in the human fetal membranes during normal gestation and parturition in the absence of infection and to show its effects on the expression of interleukin (IL)-6 and IL-8. Study Design: PBEF was immunolocalized in the fetal membranes from early pregnancy, at preterm, and at term. Its expression was quantitated by Northern analysis in separated uninfected amnion, chorion, decidua, and placenta of patients at term before labor and in full-thickness membranes before and after spontaneous labor at preterm and at term. Amnion-like epithelial (WISH) cells and fetal membrane explants were treated with recombinant PBEF (rhPBEF), and the expression of IL-6 and IL-8 was quantitated. Results: PBEF was immunolocalized throughout gestation in the amniotic epithelium and mesenchymal cells as well as the chorionic cytotrophoblast and parietal decidua. Northern analysis showed significantly more (P <.01) PBEF expressed in the amnion than in either chorion or placenta. Its expression increased after labor at both preterm and term and correlated with that of IL-8 (r = 0.87). rhPBEF treatment of WISH cells significantly increased IL-6 (P <.05) and IL-8 (P <.01) gene expression after 4 hours and of IL-8 protein after 24 hours (P <.01); similar 4-hour treatment of fetal membrane explants significantly increased IL-6 (P <.01) and IL-8 (P <.05) gene expression. Conclusion: PBEF is a novel cytokine constitutively expressed by the fetal membranes during pregnancy. It increased the expression of IL-6 and IL-8 and may be important in both normal spontaneous labor and infection-induced preterm labor. (Am J Obstet Gynecol 2002;187:1051-8.)
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☆Supported by National Institutes of Health grant No. HD23314 (G. D. B.-G.) and by grants No. RR-03061 and P20RR 11091 to the University of Hawaii and Kapiolani Medical Center under the Research Centers in Minority Institutions Program of the National Center for Research Resources.
☆☆Reprint requests: G. Bryant-Greenwood, PhD, Pacific Biomedical Research Center, University of Hawaii, 1993 East West Rd, Honolulu, HI 96822. E-mail: gbg@pbrc.hawaii.edu
