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1 August 2002 Nuclear Factor Kappa B Regulation of Proinflammatory Cytokines in Human Gestational Tissues In Vitro
Martha Lappas, Michael Permezel, Harry M. Georgiou, Gregory E. Rice
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Abstract

Proinflammatory cytokines are implicated in the initiation and progression of human labor and delivery, particularly in relation to infection-induced preterm labor. In nongestational tissues, the nuclear factor kappa B (NF-κB) transcription pathway is a key regulator of proinflammatory cytokine release. In these tissues, sulfasalazine (SASP), through its ability to inhibit NF-κB activation, inhibits release of interleukin (IL)-2, IL-12, and tumor necrosis factor (TNF)-α. Therefore, the aim of this study was to investigate whether or not NF-κB activation regulates the formation of proinflammatory cytokines in human gestational tissues. Human placenta, amnion, and choriodecidua (n = 9 separate placentas) were incubated with 10 μg/ml of lipopolysaccharide (LPS) in the absence (control) or presence of SASP (0.1, 1, 5, or 10 mM). After 6 h of incubation, the tissues were collected, and NF-κB DNA binding activity in nuclear extracts was assessed by electromobility shift binding assay. The incubation medium was collected and the release of IL-6, IL-8, and TNF-α was quantified by ELISA. Treatment of placenta, amnion, and choriodecidua with SASP at concentrations 5 mM or greater significantly inhibited the release of IL-6, IL-8, and TNF-α, and NF-κB activation (ANOVA, P < 0.05). The data presented in this study demonstrate that the NF-κB transcription pathway is a key regulator of LPS-stimulated IL-6, IL-8, and TNF-α release from human gestational tissues. The control of NF-κB activation may therefore provide an alternative therapeutic strategy for reducing the release of proinflammatory mediators in infection associated preterm labor.

Martha Lappas, Michael Permezel, Harry M. Georgiou, and Gregory E. Rice "Nuclear Factor Kappa B Regulation of Proinflammatory Cytokines in Human Gestational Tissues In Vitro," Biology of Reproduction 67(2), 668-673, (1 August 2002). https://doi.org/10.1095/biolreprod67.2.668
Received: 9 October 2001; Accepted: 1 March 2002; Published: 1 August 2002
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