Background: Prostaglandin E2 (PGE2) is an important inflammatory mediator, which has been shown to regulate fibroblast chemotaxis and extracellular matrix production through four G-coupled protein receptors (EP1, EP2, EP3, EP4). Previous studies have linked abnormal PGE2 signaling with the development of improper damage repair and tissue fibrosis in the airway. This study begins to address the role of PGE2 in dermal fibrosis, particularly keloid formation. Such an analysis is consistent with data indicating inflammatory/immune abnormalities associated with keloids. Hypothesis: Keloid fibroblasts respond to PGE2 appropriately, but in a quantitatively diminished manner. Methods: Cultured fibroblasts from normal human skin and keloid lesions were used for these studies. Fibroblast migration was assayed using a well established two dimensional motility assay. Collagen production was analyzed using Western blot and commercial ELISA methodology. Results: Administration of PGE2 decreased keloid fibroblast migration in a dose-dependent manner, via a mechanism which appears to involve the EP2/EP4-cAMP-PKA signal transduction pathway. PGE2 reversed the transforming growth factor β-1-induced increase in collagen type I in both normal and keloid fibroblasts. Discussion: Our hypothesis is partially supported by the results, which show that the response of keloid fibroblasts to PGE2 is qualitatively and quantitatively identical to normal fibroblasts. PGE2 decreases the rates of migration and collagen synthesis of keloid fibroblasts, raising the possibility that exogenous PGE2 may have potential therapeutic applications to reduce keloid formation. Acknowledgments: The authors would like to thank Children’s Hospital of Pittsburgh for providing funding for this research.