Prematurity is one of the leading causes of infant mortality. It may result from intrauterine infection, which mediates premature labor by stimulating the production of inflammatory lipid mediators such as prostaglandin F 2␣ (PGF 2␣ ). The biological effects of PGF 2␣ are mediated via the G protein-coupled receptor FP; however, the molecular mechanism(s) of FP signaling that mediates inflammatory lipid mediator production remains unclear. We reported previously that in the human uterus, a

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... ite organ in which fibroblast, epithelial, and smooth muscle cells are the major constituents, an inverse relationship exists between the levels of PGF 2␣ and a steroid-inducible anti-inflammatory protein, uteroglobin. Here we report that, in NIH 3T3 fibroblasts and human uterine smooth muscle cells, FP signaling is mediated via multi-kinase pathways in a cell type-specific manner to activate NF-B, thus stimulating the expression of cyclooxygenase-2. Cyclooxygenase-2 is a critical enzyme for the production of prostaglandins from arachidonic acid, which is released from membrane phospholipids by phospholipase A 2 , the expression of which is also stimulated by PGF 2␣ . Most importantly, uteroglobin inhibits FP-mediated NF-B activation and cyclooxygenase-2 gene expression by binding and most likely by sequestering PGF 2␣ into its central hydrophobic cavity, thereby preventing FP-PGF 2␣ interaction and suppressing the production of inflammatory lipid mediators. We propose that uteroglobin plays important roles in maintaining homeostasis in organs that are vulnerable to inadvertent stimulation of FP-mediated inflammatory response.