Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 177, Issue 4, Pages 1755-1764Publisher
ELSEVIER SCIENCE INC
DOI: 10.2353/ajpath.2010.090781
Keywords
-
Categories
Funding
- National Institutes of Health [1-R01-HL070004-04]
- National Institute of Child Health and Human Development [1-P01-HD054713-09, 5R01HD056123-02]
- March of Dimes Foundation [21-FY05-1249]
Ask authors/readers for more resources
Chorioamnionitis frequently precedes both genital tract and placental inflammation and is both a primary cause of maternal morbidity and a major antecedent of preterm premature rupture of the membranes (PPROM) as well as preterm delivery (PTD). In most cases of chorioamnionitis, neutrophils dominate the decidua. In a subset of these cases, a predominance of monocytes is uniquely associated with both neonatal intraventricular hemorrhage and death. The multifunctional cytokine, interleukin-6, promotes local monocyte dominance via several mechanisms. In this study, immunostaining of placental sections revealed significantly higher interleukin-6 HSCOREs in decidual cells (DCs) but not in interstitial trophoblasts, in chorioamnionitis versus gestational age-matched control placentas (P < 0.05). In confluent leukocyte-free term DCs, secreted interleukin-6 levels in incubations with estradiol-17 beta were increased 2500-fold by IL-1 beta (P < 0.05). This up-regulation was inhibited by more than 50% in parallel incubations that included medroxyprogesterone acetate (n = 12, P < 0.05). Western blotting data confirmed these enzyme-linked immunosorbent assay results; quantitative RT-PCR findings demonstrated corresponding changes in interleukin-6 mRNA levels. Specific inhibitors of signaling for both nuclear factor-kappa B activation and p38-mitogen-activated protein kinase, but not for protein kinase C, significantly decreased IL-1 beta-enhanced interleukin-6 expression levels in cultured DCs. In conclusion, in situ and in vitro results indicate that significantly enhanced interleukin-6 expression levels in DCs during chorioamnionitis could be pivotal in skewing decidual monocyte differentiation to macrophages. (Am J Pathol 2010, 1 77:1755-1764; DOI: 10.2353/ajpath.2010.090781)
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available