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Mechanisms of Leukocyte Accumulation and Activation in Chorioamnionitis: Interleukin 1β and Tumor Necrosis Factor Enhance Colony Stimulating Factor 2 Expression in Term Decidua

Department of Human Pathology and Oncology, University of Siena, Italy

Paolo Toti, MD

Department of Human Pathology and Oncology, University of Siena, Italy

Lynn Buchwalder, MS

Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut

Alessandra Casciaro, MS

Department of Human Pathology and Oncology, University of Siena, Italy

Marcella Cintorino, MD

Department of Human Pathology and Oncology, University of Siena, Italy

Frederick Schatz, PhD

Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut, frederick.schatz{at}yale.edu

Basya Rybalov, PhD

Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts

Charles J. Lockwood, MD

Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut

Chorioamnionitis is a major cause of prematurity as well as perinatal morbidity and mortality. The present study observed a marked increase in immunohistochemical staining for Colony Stimulating Factor 2 (CSF2; also known as granulocyte macrophage-colony stimulating factor), a potent neutrophil and macrophage chemoattractant and activator, in the decidua of patients with CAM compared with controls (n = 8; P = .001). To examine the regulation of this CSF2, cultured decidual cells primed with estradiol (E₂) or E₂ plus medroxyprogesterone acetate, were exposed to tumor necrosis factor- or interleukin-1β and secreted CSF2 measured by ELISA. Levels of CSF2 in E₂ plus MPA-treated cultures increased 18- and 245-fold following treatment with TNF or IL1B (n = 7, P < .05). Quantitative RT-PCR demonstrated parallel changes in mRNA levels. This study reveals that CSF2 is strongly expressed in decidua from patients with CAM and indicates TNF or IL1B as important regulators of CAM-related decidual leukocyte infiltration and activation.

Key Words: CSF2 • GM-CSF • chorioamnionitis • TNF-a • IL-1β.

This version was published on May 1, 2009

Reproductive Sciences, Vol. 16, No. 5, 453-461 (2009)
DOI: 10.1177/1933719108328609


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