REGULATION OF INTERLEUKIN-6 AND INTERLEUKIN-1-BETA GENE-EXPRESSION INTHE MOUSE DECIDUUM

Expression and regulation of interleukin-6 (IL-6) and IL-1 beta were e xamined in the mouse deciduum and in experimentally induced deciduoma from 6 to 8 days postcoitum (1 dpc = vaginal plug), as well as in cult ured mouse decidual cell preparations. Levels of these mRNAs in the de ciduum and deciduoma were below the limits of detection by Northern bl otting. However, enzymatic dispersion and culture of decidual cells an d/or exposure to bacterial endotoxin-lipopolysaccharide (LPS) induced these mRNAs. IL-6 levels that accumulated in the culture medium (3990 pg/3 x 10(6) cells/day) were about 90-times higher than those of IL-1 beta (45 pg/3 x 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-1 beta mRNA s and proteins. In vivo, few IL-1 beta immunopositive cells were local ized 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 implanta tion site. LPS rapidly induced interleukin mRNAs in the deciduum and d eciduoma, After LPS injection, IL-1 beta immunopositive cells were dis persed in the myometrium and mesometrial deciduum. In contrast, after LPS injection (2 h), IL-6 mRNA was abundant in 'cords' of cells that t raverse the mesometrial deciduum longitudinally, as well as in cells d ispersed throughout the myometrium. Thus, the IL-1 beta and IL-6 genes are expressed and regulated in distinct subsets of cells in the decid ual bed. The pattern of F4/80 immunostaining is consistent with macrop hages as the major, if not only, source of decidual IL-1 beta IL-6 is also expressed in these cells. However, IL-6 gene expression is regula ted in a distinct subset of cells located in the mesometrial decidual bed of the mouse.