Interleukin-1 Stimulates Human Uterine Prostaglandin Production Through Induction of Cyclooxygenase-2 Expression

Authors

  • PHILLIP N. RAUK,

    1. Magee-Womens Research Institute and the Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA 15213
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  • JYE-PING CHIAO

    1. Magee-Womens Research Institute and the Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA 15213
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Address reprint requests to Phillip N. Rauk, M.D., Magee-Womens Research Institute, 204 Craft Avenue, Pittsburgh, PA 15213.

E-mail: rsipnr@mail.magee.edu

Abstract

PROBLEM: Uterine infection occurs in as much as 20% of preterm labor and results in increased decidual cytokines. The objective of this study was to examine the effect of interleukin-1 (IL-1) and the cyclooxygenase-2 (COX-2) inhibitor, NS-398, on myometrial prostaglandin (PG) production and COX-2 expression.
METHOD OF STUDY: Human uterine myocytes were stimulated with IL-1 (0–50 ng/mL) over 24 hr. PGE2, PGF, and 6-keto F were measured by enzyme-linked immunosorbent assay. Both COX-1 and COX-2 proteins and mRNA were measured by western and northern blot, respectively.
RESULTS: IL-1 increased PG production beginning at 6 hr. COX-2 protein increased beginning at 4 hr and continued to increase at 24 hr. COX-2 mRNA increased at 2 hr and peaked at 4 hr. NS-398 blocked PG production but had no effect on COX-2 protein or mRNA.
CONCLUSIONS: IL-1 increases PG production by myometrium by increased COX-2 expression. NS-398 completely blocks IL-1-induced PG production. With intrauterine infection, IL-1 may induce labor through the autocrine production of uterotonic PGs.

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