Regulation of interleukin-6 and interleukin-1β gene expression in the mouse deciduum

Abstract

Expression and regulation of interleukin-6 (IL-6) and IL-1β were examined in the mouse deciduum and in experimentally induced deciduoma from 6 to 8 days postcoitum (1 dpc = vaginal plug), as well as in cultured mouse decidual cell preparations. Levels of these mRNAs in the deciduum and deciduoma were below the limits of detection by Northern blotting. However, enzymatic dispersion and culture of decidual cells and/or exposure to bacterial endotoxin-lipopolysaccharide (LPS) induced these mRNAs. IL-6 levels that accumulated in the culture medium (3990 pg/3 × 10 6 cells/day) were about 90-times higher than those of IL-1β (45 pg/3 × 10 6 cells/day). Progesterone (10 −7 M) modestly (40%) reduced the levels of IL-6 mRNA and protein during culture, whereas LPS dramatically (8-fold) and rapidly induced IL-6 and IL-1β mRNAs and proteins. In vivo, few IL-1β immunopositive cells were localized by immunohistochemistry in the 8 dpc deciduum. In contrast, IL-6 mRNA was localized by in situ hybridization in dispersed clusters of a few cells in the mesometrial deciduum near the center of the implantation site. LPS rapidly induced interleukin mRNAs in the deciduum and deciduoma. After LPS injection, IL-1β immunopositive cells were dispersed in the myometrium and mesometrial deciduum. In contrast, after LPS injection (2 h), IL-6 mRNA was abundant in ‘cords’ of cells that traverse the mesometrial deciduum longitudinally, as well as in cells dispersed throughout the myometrium. Thus, the IL-1β and IL-6 genes are expressed and regulated in distinct subsets of cells in the decidual bed. The pattern of F4/80 immunostaining is consistent with macrophages as the major, if not only, source of decidual IL-1β. IL-6 is also expressed in these cells. However, IL-6 gene expression is regulated in a distinct subset of cells located in the mesometrial decidual bed of the mouse.