Regulated on activation, normal T-cell-expressed and -secreted mRNA expression in normal endometrium and endometriotic implants - Assessment of autocrine/paracrine regulation by in situ hybridization

Chemoattraction of macrophages and T cells into the normal endometrium and inflammatory sites within endometriotic foci is mediated by chemokine gene expression. mRNA transcripts encoding regulated on activation, normal T-cel l-expressed and -secreted (RANTES), a monocyte and T-cell chemokine, were d emonstrated in the stroma of normal endometrium and endometriotic implants using in situ mRNA hybridization, Epithelial glands failed to express RANTE S mRNA. In histological serial sections, we observed CD68-positive macropha ges in the stroma of endometriotic implants adjacent to regions with promin ent RANTES mRNA hybridization, In adjacent sections, monoclonal antibodies against tumor necrosis factor (TNF)-alpha showed this cytokine to be locali zed to stromal and epithelial compartments of the endometriotic implant wit h weak staining in unaffected ovarian tissue, Subconfluent monolayers of en dometriotic stromal cells were tested for RANTES gene expression in situ, b ut we could only detect RANTES mRNA in isolated stromal cells after treatme nt with TNF-alpha. No RANTES mRNA was observed in unstimulated stromal cell s or TNF-alpha stimulated or unstimulated epithelial cells, The data are co nsistent with a model in which proinflammatory cytokines (eg, TNF-alpha) in duce RANTES gene expression limited to specific cells within endometrial an d endometriotic stroma, Production of this chemokine, in turn, stimulates r ecruitment of CD68-positive macrophages into these tissues.