Interleukin-1 (IL-1) is well known to be involved in the immune system and have a role in ovarian inflammation as well as exhibiting inhibitory effects on steroidogenesis and folliculogenesis. Since multiple ascpects of ovarian function have also been shown to involve cytokine/chemokine networks, IL-1-induced chemokine gene expression in mouse granulosa cells was investigated. Granulosa cells from immature mice at 28 days of age were cultured with IL-1 (10 ng/ml). IL-1 induced abundantly and specifically keratinocyte chemoattractant (KC) chemokine, a CXC subfamily. KC chemokine mRNA and protein were increased 1-2 h after IL-1 and then gradually decreased. The KC promoter (-701/+30) containing three nuclear factor (NF)-B sites was fully responsive to IL-1 whereas deletions and mutants of the NF-B sites lowered the responsiveness to IL-1. The proximal NF-B site (-69/-59) played a critical role in regulating IL-1-induced KC chemokine promoter activity. Overexpression of the inhibitor of NF-B (IB) blocked KC promoter activity induced by IL-1 whereas overexpression of p65, a component of NF-B, increased promoter activity and mRNA of KC chemokine. In addition, FSH (FSH) did not affect NF-B signaling or IL-1-induced KC chemokine promoter activity. Within 1-3 h after ip injection of lipopolysaccharide (LPS, 100 µg/mouse), a product known to stimulate release of IL-1, KC chemokine was localized in the ovary to granulosa cells as well as the thecal-interstitial layer. The results of this study indicate that KC gene is a chemokine induced acutely by IL-1 via NF-B signaling in mouse granulosa cells.